Systems and methods for treating eye diseases

ABSTRACT

A method may include accessing a terminal branch of an ophthalmic artery through a face of a subject. Additionally, the method may include positioning a device within the ophthalmic artery of the subject and treating at least one of a blockage, a stenosis, a lesion, plaque or other physiology in at least one of the ophthalmic artery or a junction between an internal carotid artery and the ophthalmic artery.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.15/971,809, which is a continuation of U.S. application Ser. No.15/681,075, filed on Aug. 18, 2017, now U.S. Pat. No. 9,987,164, whichis a continuation application of International Application No.PCT/US2017/021673, filed on Mar. 9, 2017, which claims the benefit ofpriority of U.S. Provisional Application No. 62/396,091, filed on Sep.16, 2016, U.S. Provisional Application No. 62/314,340, filed on Mar. 28,2016, and U.S. Provisional Application No. 62/305,991, filed on Mar. 9,2016, all of which are incorporated by reference herein in theirentireties. This application also claims priority to U.S. applicationSer. No. 15/609,547, filed on May 31, 2017, which is a continuation ofU.S. application Ser. No. 14/385,496, filed on Sep. 15, 2014, which isthe U.S. National Stage Application of International Application No.PCT/US2013/053670, filed on Aug. 5, 2013, which claims the benefit ofpriority of U.S. Provisional Application No. 61/679,351, filed on Aug.3, 2012, all of which are incorporated by reference herein in theirentireties. This application also claims priority to InternationalApplication No. PCT/US2017/051551, filed on Sep. 14, 2017, which claimsthe benefit of priority of U.S. Provisional Application No. 62/395,294,filed on Sep. 15, 2016, and U.S. Provisional Application No. 62/396,091,filed on Sep. 16, 2016, all of which are incorporated by referenceherein in their entireties.

TECHNICAL FIELD

The present disclosure relates to treating an eye, including diseasesand other conditions of the eye.

BACKGROUND

Diseases of the eye, specifically age-related macular degeneration(AMD), glaucoma, and diabetic retinopathy affect a large percentage ofthe population. However, current therapies are deficient in one or moreaspects, necessitating improved approaches. The present disclosureaddresses some or all of the problems found in current therapies.

BRIEF SUMMARY

The present disclosure is directed to treating an eye by using a device,method, system, or assembly as described herein. Specifically, thepresent disclosure is directed to treating eye diseases or conditions byusing a device, method, system, or assembly as described herein.

For example, a method of the present disclosure may include accessing aterminal branch of an ophthalmic artery (OA) through a face of asubject, positioning a device within the OA of the subject, and treatingat least one of a blockage, a stenosis, a lesion, plaque, or otherphysiology in at least one of the OA or a junction between an internalcarotid artery (ICA) and the OA.

Examples of the method may include any one or more of the followingfeatures. The method may include inducing retrograde blood flow in theOA. The treating may include increasing a blood flow rate in the OA. Thetreating may include increasing a size of the at least one of the ICA orthe OA. The increasing the size of the at least one of the OA or thejunction between the ICA and the OA includes removing material. Theincreasing the size of the at least one of the OA or the junctionbetween the ICA and the OA includes using a balloon in a balloondilation procedure. The method may further include measuring a bloodflow rate in the OA. The measuring the blood flow rate in the OA mayinclude at least one of measuring a linear blood flow rate or avolumetric blood flow rate. The method may further include stoppingantegrade blood flow in the OA. The accessing the terminal branch of theOA through the face of the subject may include accessing the OA througha facial skin of the subject. The accessing the terminal branch of theOA through the face of the subject includes accessing a supraorbitalartery (SOA) or a supratrochlear artery (STA) of the subject.

In a further example, a method may include positioning a first device ina terminal branch of an OA through a face of a subject. Further, themethod may include stopping antegrade flow in the OA and treating atleast one of a blockage, a stenosis, a lesion, plaque, or otherphysiology in at least one of the OA or a junction between the ICA andthe OA.

Examples of the method may include any one or more of the followingfeatures. The method may include inducing retrograde blood flow. Themethod positioning the first device in a terminal branch of the OAthrough the face of the subject may include positioning the first devicein at least one of a SOA or a STA. The treating may include increasing ablood flow rate in the OA. The treating may include increasing a size ofthe at least one of the OA or the junction between the ICA and the OA.The increasing the size of the at least one of the OA or the junctionbetween the ICA and the OA may include removing material. The increasingthe size of the at least one of the OA or the junction between the ICAand the OA may include using a balloon. The method may include measuringa blood flow rate in the OA. The measuring the blood flow rate mayinclude measuring at least one of a linear blood flow rate or avolumetric blood flow rate.

In a further example, a method may include locating a site in anarterial blood supply to an eye that compromises blood flow andcontributes to an eye disorder. The method may further include accessinga terminal branch of an OA through a face of a subject and delivering afirst device intravascularly to the site. Additionally, the method mayinclude treating the site with the first device.

Examples of the method may include any one or more of the followingfeatures. The site may be in at least one of an OA or a junction betweenan ICA and the OA. The method may include at least one of stoppingantegrade blood flow in the OA or inducing retrograde blood flow in theOA.

The present disclosure also includes intravascular medical devices andmethods intended to sufficiently unblock or partially restore blood flowin a blocked or partially blocked artery such that nutrient(s) contentis increased distal to the blockage. An embodiment of the disclosure isdirected to devices and methods for restoring blood flow through theostium. Another embodiment of the disclosure includes using thesedevices and methods to restore or increase blood flow to the eye or aportion thereof. Another embodiment includes restoring or increasingnutrient levels in the eye or a portion thereof. Restoring or increasingblood flow may include using these devices and methods, or equivalentdevices and methods, but is not to be limited thereby.

The present disclosure also includes methods and devices for OAinterventional procedures, such as stenting, angioplasty, andatherectomy, performed through a transcervical or transfemoral approachinto the OA, either using an open surgical technique or using apercutaneous technique, such as a modified Seldinger technique. Some ofthese methods and devices are particularly useful in procedures whichuse reverse or retrograde blood flow.

For example, the disclosed methods and devices may include arterialaccess sheaths, closure devices, and interventional catheters. Thesemethods and devices are useful for procedures utilizing any method ofembolic protection, including distal filters, flow occlusion, retrogradeflow, or combinations of these methods, or for procedures which do notuse any method of embolic protection. Specific methods and devices forembolic protection are also described.

In other examples, the present disclosure describes methods and devicesfor enabling retrograde or reverse flow blood circulation in the OA inorder to limit or prevent the release of emboli into the eye, and/or toemploy various procedures for establishing, restoring, or increasingblood flow to the eye.

The present disclosure also describes a method for treating an OA,comprising forming a penetration in a wall of a carotid artery;positioning an arterial access sheath through the penetration; andcausing retrograde blood flow from the OA into the sheath. In someembodiments, the method may also include inserting a delivery catheterthrough the sheath into a treatment site comprised of the ICA, theostium, the junction between the ICA and the OA, the portion of the OAnear the ICA, and/or the OA. In this aspect, causing retrograde flow maycomprise connecting the arterial access sheath to a passive flowreversal circuit, or it may comprise connecting the arterial accesssheath to an active aspiration source such as a syringe or suction pump.

In one example, the present disclosure includes a method of inducingretrograde blood flow which may include inserting a first arterialdevice into at least one of an ICA or a common carotid artery (CCA) of asubject. Additionally, the method may include inserting a secondarterial device into a terminal branch of an OA of the subject. Further,the method may include inducing retrograde blood flow into the firstarterial sheath and delivering at least some of the induced retrogradeblood flow through the second arterial device and into the terminalbranch of the OA.

Examples of the method may include any one or more of the followingfeatures. The inducing retrograde blood flow may include expanding anocclusion device of the first arterial device or compressing the atleast one of the ICA or the CCA against a surface of the first arterialdevice. The method may further include inserting a vascular devicewithin a vein of the subject. The vein may be an internal jugular vein(IJV) of the subject. The occlusion device may be a balloon. The inducedretrograde blood flow may include retrograde blood flow within the OA ofthe subject. Inserting at least one of the first arterial device or thesecond arterial device may include insertion through a skin of a face ofthe subject. Inserting the second arterial device into a terminal branchof the OA of the subject may include insertion within at least one of aSOA, STA, a dorsal nasal artery (DNA), or a facial artery (FA) of thesubject.

In some examples, the method of inducing retrograde blood flow mayinclude fluidly coupling a first device located within an arterialsystem of a subject with a second device located within a venous systemof the subject. The method may further include inducing a first flow ofblood from an OA of the subject, through the first device, through thesecond device, and into the venous system of the subject. The method mayinclude inducing a second flow of blood through the first device,through a third device located in a terminal branch of the OA of thesubject, and into the arterial system of the subject.

Examples of the method may include any one or more of the followingfeatures. The method may include treating at least one of the OA or ajunction between the ICA and the OA of the subject. The first device mayinclude an expandable portion on a distal end thereof and the method mayfurther include expanding the expandable portion to impede antegradeblood flow in at least a portion of the arterial system of the subject.The method may include compressing an arterial wall of the arterialsystem against a surface of the first device. The method may includeinserting the first device within the arterial system of the subject viaa cervical approach. The method may include inserting the third devicein at least one of a SOA, a STA, a DNA, or a FA of the subject.

The present disclosure also includes a medical system that may include afirst arterial sheath including an expandable occlusion device on adistal end thereof and a second arterial sheath configured for insertioninto a terminal branch of an OA of a subject. The system may furtherinclude a venous sheath and a stopcock. Each of the first arterialsheath, second arterial sheath, and venous sheath may be coupled to thestopcock.

Examples of the system may further include any one or more of thefollowing features. The expandable occlusion device may be a balloonconfigured to engage a wall of at least one of a CCA or the ICA of thesubject. A first conduit may extend between the stopcock and the venoussheath, and a second conduit may extend between the stopcock and thesecond arterial sheath. A filter may be positioned along the firstconduit between the stopcock and the venous sheath. The second arterialsheath may be configured for insertion within at least one of a SOA, aSTA, a DNA, or a FA of the subject.

The present disclosure also includes a system for treating an eyedisease, disorder, or condition that may include restoring or increasingan amount of blood flow to an eye, an eye portion, or a structureassociated with the eye or portion of the eye of a subject. The systemmay include a transcutaneous intervention device adapted and configuredfor ocufacial access and entry into vasculature between an ICA of theeye.

The present disclosure also includes methods, devices, and systems forremoving a blockage in the ostium or a proximal segment of the OA nearthe ICA. In these embodiments, removing the blockage comprises opening achannel or access through the ostium sufficient to provide atherapeutically beneficial result to the eye, the rear of the eye, orportions thereof. The present disclosure also includes restoring and/orimproving blood flow anywhere in the vascular pathway to or within theeye.

The present disclosure also involves restoring or improving blood flowto the eye, thereby altering the complement system. In some embodimentsof the disclosure, several CS factors, their activators, and complementregulatory proteins where identified as cardinal constituents of drusen,the hallmark extracellular retinal deposits associated with early AMD.In other embodiments of the disclosure, restoring or improving bloodflow reduces or mediates the abnormal concentration of primarycomplement factors and their activated products in the vasculature ofpatients suffering from eye diseases such as AMD and glaucoma.

In some examples of the present disclosure, restoring or improving bloodflow to the back of the eye may eliminate, reduce, or mediate CSactivation, which directly damages host tissue and recruits immune cellsto the vicinity of an active complement cascade. In other examples, thechoroid- and retinal pigment epithelium-based regulation of the CSactivity has been found to play an important role in the functions ofthe eye.

The present disclosure is also directed to devices and methods forpercutaneous access and treatment of vascular structures in the rear ofthe eye, including treatment for the symptoms related to Wet Age RelatedMacular Degeneration (WAMD) by removal of stenosis of the OA, therebyrestoring normal, or near normal, blood flow to the rear of the eye,including the retina and associated structures. The present disclosureis also related to methods and devices for selective manipulation ofintra ocular pressure (10P) be means of mechanical force for the purposeof inducing retrograde flow in the ophthalmic vasculature.

The present disclosure describes an apparatus for treating obstructionof the OA, comprising an 10P device for mechanically applying a forceagainst the front of the eye to increase 10P sufficient to temporarilystop antegrade blood flow in the ophthalmic vasculature at the back ofthe eye and thereby induce retrograde flow in the ophthalmicvasculature; an atherectomy kit for performing an atherectomy upon theOA of a patient in need thereof; and a debris capture device forplacement within the ophthalmic vasculature to capture atherectomydebris.

In another example, the present disclosure describes a device usingmechanical force selected from the group consisting of hydraulic force,pneumatic force, gravitational force, spring force, and user-appliedforce, to contact the anterior portion of the eye(s) for the purpose of10P manipulation, and wherein the apparatus is configured for use on oneeye or on both eyes simultaneously.

In another example, the apparatus may use mechanical force applied tothe anterior portion either directly or through the closed eyelid.

In another example, the apparatus may contain the capability to measurethe 10P.

In another example, the apparatus may measure the 10P using a sensorimplanted within the vitreous cavity that is capable of assessing 10Pvalues and transmitting data wirelessly.

In another example, the wireless data transmission may be provided in acontinuous and real time manner.

In another example, the 10P may be measured with a sensor temporarilyplaced within the vitreous cavity via a wired or wireless manner.

In another example, a feedback mechanism may be provided for receiving10P values (data) and providing monitoring capability.

In another example, a feedback mechanism may be provided for the generalcontrol of the 10P manipulation such that the 10P may be increased ordecreased as deemed necessary.

In another example, a feedback mechanism may be combined with a controlfunction that allows for the ability to control the rate of increaseand/or decrease of 10P as deemed necessary.

In another example, a feedback mechanism may be combined with a controlfunction such that the 10P values may be increased, decreased,maintained, or cycled as necessary.

In another example, a feedback mechanism may be combined with a controlfunction such that the rate of 10P increase, decrease, or steady statemay be controlled.

In another example, a feedback mechanism may be combined with a controlfunction such that specific parameters related to 10P values, rates offorce, and time at force may be specified and controlled.

In another example, a feedback mechanism may be combined with a controlfunction such that when specific parameters are not met, the user isinformed.

In another example, a feedback mechanism may be combined with a controlfunction such that information related to the 10P value is displayed forthe user to see.

In another example, a feedback mechanism may be combined with a controlfunction such that the data may be displayed, manipulated, and/orcaptured in a method for record keeping.

The present disclosure also includes a method of treating obstruction ofthe OA, comprising the steps of inducing retrograde flow in theophthalmic vasculature by applying a mechanical force against the frontof the eye to increase 10P sufficient to temporarily stop antegradeblood flow in the ophthalmic vasculature at the back of the eye;performing an atherectomy upon the OA of a patient in need thereofduring retrograde blood flow; and deploying a debris capture devicewithin the ophthalmic vasculature to capture atherectomy debris, whereinthe retrograde flow blocks the debris from the atherectomy from flowingdownstream and causing an ischemic event.

In another example, there is provided wherein the retinal arteries mayflow in reverse for a predetermined timeframe.

In another example, there is provided wherein intravascular debriswithin the retinal artery may flow in reverse for a predetermined amountof time.

In another example, there is provided wherein the ophthalmic arteriesmay flow in reverse for a predetermined timeframe.

In another example, there is provided wherein intravascular debriswithin the OA may flow in reverse for a predetermined amount of time.

In another example, there is provided use in conjunction with aninterventional device placed within the target anatomy for the purposeof tissue removal e.g., stenosis, lesions, etc.

In another example, there is provided wherein debris is captured byplacement of a capture device placed within the target anatomy.

In another example, there is provided a tissue removal device fortreating obstruction of the OA, comprising: a percutaneously deliveredtapered corewire ranging in diameter from about 0.19 mm to about 0.88mm, the corewire disposed within a delivery sheath, said corewire havinga tissue cutting element at or near a distal end, said corewire havingan integral inflatable balloon section at the distal end as a protectiveelement, and said corewire having an atraumatic tip.

In another example, the device may be configured for percutaneous accessof the ICA.

In another example, the device may be configured for percutaneous accessof the OA.

In another example, the device may be configured to be visible usingnon-invasive imaging techniques (e.g., fluoroscopy).

In another example, the device may include distal emboli protection.

In another example, there is provided a flow direction device to aid inthe positioning of the device within the target anatomy.

In another example, there is provided a flow direction device that mayuse reverse flow to aid in the removal of the device from within thetarget anatomy during selectively induced retrograde flow.

In another example, there is provided a specifically shaped guidewire toaccess the OA from the ICA.

In another example, there is provided a specifically designed guidingcatheter to access the OA from the ICA.

In another example, there is provided a specifically shaped guidewire toaccess the OA from the ICA, through the guiding catheter, once theguiding catheter has transited the OA, wherein this guidewire isconfigured to gain further downstream OA access without disturbance ofvessel physiology due to guidewire tip shape.

In another example, there is provided a downstream protection elementfor downstream protection in the ICA.

In another example, a method of the present disclosure may use a shapedtip guidewire, a straight tip guidewire, and a guiding catheter,comprising the steps in which the straight tip guidewire is used alone,or in conjunction with the guiding catheter to access the OA from theICA, wherein once the OA has been cannulated, the shaped tip guidewireis exchanged for the straight tip guidewire for the balance of theprocedure. Further, once the OA has been cannulated, the shaped tipguidewire is exchanged with an interventional device for the balance ofthe procedure.

In another example, there is provided an apparatus for capturingatherectomy debris as it is removed, comprising a single hypotube cut tocontain a combination atherectomy device and distal protection device.

In another example, the atherectomy device portion may fit within adelivery sheath such that the fully expanded diameter is achieved whenthe device is moved out of sheath and into the target anatomy with thefully expanded diameter at 1.4 mm, with compliance to a vessel as smallas 0.7 mm.

In another example, the atherectomy device portion may fit within adelivery sheath and the fully expanded diameter is achieved when thedevice is moved out of sheath, into the target anatomy and a central,slideable corewire is manipulated to achieve the final diameter.

In another example, the apparatus may be constructed of a solid corewirewith a mounted atherectomy and distal protection device.

In another example, the solid corewire may contain external geometryspecific to the function of performing atherectomy work.

In another example, the atherectomy portion of the apparatus may beexpandable.

In another example, the atherectomy portion of the apparatus may benon-expandable.

In another example, the atherectomy portion of the apparatus may benon-expandable, but rotatable such that rotation induces a diametricincrease in the apparatus.

In another example, the atherectomy device may fit within a deliverysheath such that the fully expanded diameter is achieved when the deviceis moved out of sheath and into the target anatomy.

In another example, the atherectomy device portion may fit within adelivery sheath such that the non expanded diameter is revealed when thedevice is moved out of sheath and into the target anatomy.

In another example, the apparatus may be constructed of a balloondesigned to inflate such that contact with the target anatomy isachieved.

In another example, the balloon may have external materials affixeddirectly to the balloon surface to facilitate atherectomy.

In another example, the balloon may have external emboli protection.

In another example, the balloon may be mounted on a polymer cathetertypical of current vascular procedure technology.

In another example, the balloon may be mounted on a solid corewire.

In another example, the balloon may be mounted on a hypotube.

In another example, there is provided a device for the removal of debrisby aspiration.

In another example, the apparatus may have a deployed, fully expandeddiameter of 1.2 mm to 1.4 mm, compressible yet effective at 0.7 mm ofdeployed diameter.

In another example, the apparatus may have a deployed, fully expandeddiameter of 1.0 mm to 1.6 mm, compressible yet effective at 0.7 mm ofdeployed diameter.

In another example, the apparatus may have a balloon shape optimized toaffect removal of material.

In another example, the apparatus may have an aspiration device forremoval of debris by aspiration via an external sheath.

In another example, the apparatus may be made of materials selected fromnitinol, stainless steel, or other materials commonly associated withintravascular medical devices.

In another example, the method may include the apparatus beingpercutaneously inserted via the ICA and navigated to the OA.

In another example, the navigation of the apparatus may be guided by useof a non-invasive imaging methodology (e.g., fluoroscopy).

In another example, distal protection may be provided for the ICA.

In another example, distal protection may be provided for the OA.

In another example, there is provided a method wherein removal of debrisby aspiration is provided for while in the OA.

In another example, there is provided a method for providing treatmentfor the symptoms related to WAMD, comprising the step of removal ofstenosis of the OA, thereby restoring normal, or near normal, blood flowto the rear of the eye, including the retina and associated structures.

In another example, there is provided a method for providing apharmaceutical based treatment for the symptoms of WAMD by delivery of apharmaceutical compound(s) specifically targeted for the treatment ofWAMD.

In another example, there is provided a method for providing apharmaceutical treatment for the medication and/or restenosis of aspecific section of the OA by delivery of a pharmaceutical compound(s)specifically targeted for the treatment of vascular lesions.

In another example, there is provided a method for providing apharmaceutical treatment for the prevention and/or treatment of thrombusor thrombus related conditions in a specific section of the OA bydelivery of a pharmaceutical compound(s) specifically targeted for thetreatment of thrombus or thrombus related conditions.

In another example, there is provided an apparatus for providing apharmaceutical based treatment for the symptoms of WAMD by physicaldelivery of a pharmaceutical compound(s) specifically targeted for thetreatment of WAMD.

In another example, there is provided an apparatus for providing apharmaceutical treatment for the medication and/or restenosis of aspecific section of the OA by physical delivery of a pharmaceuticalcompound(s) specifically targeted for the treatment of vascular lesions.

In another example, there is provided an apparatus for providing apharmaceutical treatment for the prevention and/or treatment of thrombusor thrombus related conditions in a specific section of the OA byphysical delivery of a pharmaceutical compound(s) specifically targetedfor the treatment of thrombus or thrombus related conditions.

In another example, the apparatus may be packaged within a single unit,containing a hybrid catheter and flow directed balloon.

In another example, there is provided an apparatus wherein the OD ofsingle unit being 6-9 French at the thicker, proximal end of the hybridcatheter/balloon with the distal 2-5 cm of the apparatus being 0.12 mmto 0.19 mm in diameter of a flow directed guidewire with the finaldistal portion of the apparatus being 8 mm to 15 mm of the apparatusbeing a flow directed balloon.

In another example, there is provided an apparatus wherein the flowdirected balloon inflates from a minimum of 0.7 mm to a maximum of 1.4mm.

In another example, the apparatus may coat the balloon with a drug fordelivery and compression into the wall of the arterial source with thestenotic lesion.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary system of devices for transcervical OAprocedures using a retrograde blood flow embolic protection system,wherein an arterial access device accesses the OA via a transcervicalapproach and a venous return device communicates with the IJV, accordingto an aspect of the present disclosure.

FIG. 2 illustrates an embodiment of an arterial access device, accordingto an aspect of the present disclosure.

FIGS. 3A and 3B illustrate exemplary vasculature of the eye of asubject.

FIG. 4 illustrates an exemplary reverse flow system according to anaspect of the present disclosure.

FIG. 5 illustrates an exemplary sheath and flow direction balloon withinan ICA, according to an aspect of the present disclosure.

FIG. 6 illustrates an exemplary sheath within an ICA, and a flowdirection element about the artery, according to an aspect of thepresent disclosure.

FIGS. 7A and 7B illustrate an exemplary semi-transparent perspectiveside view of an embodiment, according to an aspect of the presentdisclosure.

FIG. 8 is an exemplary semi-transparent perspective side view of anotherembodiment of the present disclosure.

FIG. 9A illustrates an exemplary corewire and FIG. 9B illustrates anexemplary tapered corewire, according to an aspect of the presentdisclosure.

FIG. 10 illustrates an exemplary side view of an embodiment of thepresent disclosure.

FIGS. 11A and 11B illustrate exemplary before and after side views of anembodiment of the present disclosure.

FIG. 11C illustrates an exemplary side view of an embodiment of thepresent disclosure.

FIGS. 12A and 12B illustrate exemplary before and after side views of anembodiment of the present disclosure.

FIGS. 13A-13C illustrate an exemplary hypotube atherectomy corewire andexpanded atherectomy balloon with a distal protection element.

FIGS. 14A and 14B illustrate exemplary side view line drawings of amulticomponent apparatus of the present disclosure.

FIGS. 15A and 15B illustrate exemplary before and after side views of anembodiment of the present disclosure.

FIGS. 16A-16C illustrate exemplary variations in balloon distalelements, according to an aspect of the present disclosure.

FIGS. 17A-17C illustrate an exemplary series of sequential line drawingsshowing use of shaped and straight guide wires, according to an aspectof the present disclosure.

FIG. 18 illustrates an exemplary side view line drawing of an embodimenthaving an inflatable balloon and a intravascular positioningdevice/parachute, according to an aspect of the present disclosure.

FIG. 19 illustrates an exemplary side view line drawing of an embodimenthaving an inflatable balloon and a intravascular positioningdevice/parachute, according to an aspect of the present disclosure.

FIG. 20 illustrates an exemplary side view line drawing of an embodimenthaving an inflatable balloon and a intravascular positioningdevice/parachute, according to an aspect of the present disclosure.

FIG. 21 illustrates an exemplary side view line drawing of an embodimenthaving an inflatable balloon, according to an aspect of the presentdisclosure.

FIG. 22 illustrates an exemplary side view line drawing of an embodimenthaving an inflatable balloon, according to an aspect of the presentdisclosure.

FIGS. 23A-23E illustrate an exemplary series of figures showing anatomyand use of an 10P device, according to an aspect of the presentdisclosure.

FIGS. 24A and 24B illustrate exemplary side view line drawings of theeye showing 10P caused by mechanical force, according to an aspect ofthe present disclosure.

FIG. 25 illustrates an exemplary front view line drawing of the eyeshowing 10P caused by mechanical force, with a controller unit forinteracting in a continuous or periodic manner, according to an aspectof the present disclosure.

FIG. 26 is an exemplary anatomical drawing of the eye for referencepurposes only.

DETAILED DESCRIPTION

Both the foregoing general description and the following detaileddescription are exemplary and explanatory only and are not restrictiveof the features, as claimed.

The singular forms “a,” “an,” and “the” include plural reference unlessthe context dictates otherwise. The terms “approximately” and “about”refer to being nearly the same as a referenced number or value. As usedherein, the terms “approximately,” “about,” and “substantially,”generally should be understood to encompass ±5% of a specified amount orvalue, unless otherwise stated.

As used herein, the terms “comprises,” “comprising,” “having,”“including,” or other variations thereof, are intended to cover anon-exclusive inclusion such that a process, method, article, orapparatus that comprises a list of elements does not include only thoseelements, but may include other elements not expressly listed orinherent to such a process, method, article, or apparatus. Additionally,the term “exemplary” is used herein in the sense of “example,” ratherthan “ideal.”

The terms “proximal” and “distal” are used herein to refer to therelative positions of the components of an exemplary medical device orinsertion device. When used herein, “proximal” refers to a positionrelatively closer to the exterior of the body or closer to a medicalprofessional using the medical device or insertion device. In contrast,“distal” refers to a position relatively further away from the medicalprofessional using the medical device or insertion device, or closer tothe interior of the body.

The terms “downstream” or “antegrade” and “upstream” or “retrograde,”when used herein in relation to the subject's vasculature, referrespectively, to the direction of blood flow and the direction oppositethat of blood flow, respectively. In the arterial system, “downstream”or “antegrade” refers to the direction further from the heart, while“upstream” or “retrograde” refers to the direction closer to the heart.

As used herein, “embolic debris” means any biologic or non-biologicmass, the presence of which in the vasculature may present a risk,including, but not limited to, plaque, emboli, etc.

“Nutrients” as used herein includes, but is not limited to, oxygen,hemoglobin, complement, and glucose.

As used herein, “therapeutically beneficial result” refers to anyperceived or actual benefit to the patient. Examples of beneficialresults include, but are not limited to, treatment of an eye disease,condition, and/or symptom; restoring or increasing blood flow in anymanner that treats an eye disease, condition, and/or symptom; andremoving or partially removing a blockage in the blood flow path betweenthe heart and the eye, preferably in the OA or a portion thereof.

In this disclosure, “reverse flow, “retrograde flow,” and “retrogradeblood flow” are used synonymously. As used herein, reverse flow orretrograde flow is the flow of blood opposite to the direction of bloodflow under normal blood flow conditions, and refers to the consequencesof blocking blood flow in an artery and establishing a fluid flowconnection with a vein. Under these conditions, the natural pressuregradient differential causes blood to flow in a reverse direction in theartery. For example, when flow through the ICA is blocked, the naturalpressure gradient between the ICA and the venous system causes blood toflow in a retrograde or reverse direction from the vasculature of theeye, through the OA, and through the ICA. Reverse flow may be achievedby creating a pressure gradient so blood flow is reversed and directed,for example, from the treatment site into a lumen of a catheter to bererouted to another location. The pressure gradient can be facilitatedby creating a low-pressure source(s), which can be within the catheteritself or created in a desired location within the vasculature that isin fluid communication with the lumen of the catheter.

In a reverse flow embolic protection method, an arterial access cannulamay be connected to a venous cannula in order to establish a reverse orretrograde flow from an artery (such as the ICA and/or OA) through thearterial cannula and away from the eye and/or vasculature of the eye.Flow in an artery is occluded, typically by inflating a balloon on thedistal tip of the cannula, in a carotid artery, the ICA, or the OA,thereby reversing blood flow in the ICA and/or the OA. After suchreverse or retrograde flow is established, any catheter orinterventional procedure in the OA can be performed with a greatlyreduced risk of emboli entering the eye.

As used herein, “blockage” refers to complete or partial blockage;reduced, restricted, or eliminated blood flow; sometimes caused byplaque, tortuous shaped anatomy, vessel failure, or dysfunction. Withoutintending to be bound by theory, it is believed that any blockage orreduction in fluid or blood flow is a mediator of certain consequencesdescribed more particularly below, and that any condition, such as ablockage, that leads to lowered nutrient availability and/or consumptionis a direct mediator of normal physiologic function. It is also believedthat those conditions also mediate metabolic waste removal from cells,organs, and other biological structures.

In accordance with this disclosure, possible eye diseases or conditionsinclude, but are not limited to, one or more of the following: reducedor blocked blood flow in one or more arteries or system of arteries;reduced or blocked source of energy or nutrients to a cell, organelle ofa cell, mitochondrion, group of cells, or organ; altered aerobic energymetabolism; altered mitochondria oxidative phosphorylation; decreased orblocked supply of glucose; altered aerobic energy metabolism;photoreceptor dysfunction and degeneration; altered energy homeostasis;glucose; glucose and oxygen; mitochondrial damage; one or morecombinations of substrates, including, but not limited to, glucose,pyruvate, lactate, L-glutamine, and p-hydroxybutyrate; alteredmitochondria oxidative phosphorylation; complement; any molecule in thecomplement cascade; and localized drug and/or an oxygen device forincreasing flow or amount of oxygen in one or more eye tissues;decreased hemoglobin amount or delivery to one or more intra-cranialstructures or to one or more eye tissues; reduced or blocked blood flowor rate anywhere in the fluid flow path between the ICA and eye tissue;and any blockage or partial blockage in one or more arteries or systemof arteries; any mediation of the complement system, the complementcascade, and/or one of the complement cascade associated molecules; andlowered/blocked nutrient supply and/or metabolic waste removal isimplicated, and therefore may mediate one or more diseases, disorders,or biological function.

These conditions may occur in one or more of the following areas orstructures, including, but not limited to: one or more arteries; one ormore cranial arteries; one or more arteries associated with supplyingblood flow to the eye; the ICA; the OA; anywhere in the fluid flow pathbetween the ICA and eye tissue; the junction between the ICA and the OA,which is referred to in this disclosure as the ostium; and secondaryareas of the anatomy, which include the vascular system commonlyreferred to as the terminal branches. These secondary areas include, butare not limited to the SOA, the STA, the DNA, the FA; any cranialartery; and in any of the junctions or ostia between any of thevasculature between the ICA and one or more eye tissues.

Examples of eye diseases and conditions include, but are not limited to:AMD (both dry and wet); neuronal cell death; Alzheimer's disease;dementia; glaucoma; diabetic macula edema; macular telangiectasia (e.g.,type 1 or 2 macular telangiectasia); atrophic macular degeneration;chorioretinopathy (e.g., central serous chorioretinopathy); retinalinflammatory vasculopathy; pathological retinal angiogenesis;age-related maculopathy; retinoblastoma; Pseudoxanthoma elasticum; avitreoretinal disease; choroidal sub-retinal neovascularization; centralserous chorioretinopathy; ischemic retinopathy; hypertensive retinopathyor diabetic retinopathy (e.g., nonproliferative or proliferativediabetic retinopathy, such as macular edema or macular ischemia);retinopathy of prematurity (e.g., associated with abnormal growth ofblood vessels in the vascular bed supporting the developing retina);venous occlusive disease (e.g., a retinal vein occlusion, branch retinalvein occlusion or central retinal vein occlusion); arterial occlusivedisease (e.g., branch retinal artery occlusion (BRAO); central retinalartery occlusion or ocular ischemic syndrome); central serouschorioretinopathy (CSC); cystoid macular edema (CME) (e.g., affectingthe central retina or macula, or after cataract surgery); retinaltelangiectasia (e.g., characterized by dilation and tortuosity ofretinal vessels and formation of multiple aneurysms, idiopathic JXT,Leber's miliary aneurysms, or Coats' disease); arterial macroaneurysm;retinal angiomatosis; radiation-induced retinopathy (RIRP); or rubeosisiridis (e.g., associated with the formation of neovascular glaucoma,diabetic retinopathy, central retinal vein occlusion, ocular ischemicsyndrome, or chronic retinal detachment); distortions and/or blind spots(scotoma); changes in dark adaptation (diagnostic of rod cell health);changes in color interpretation (diagnostic of cone cell health);decrease in visual acuity; and cataracts (e.g., age-related cataract).

In a general sense, the pathogenesis of some of these eye diseases issimilar if not the same as those seen for cardiac diseases and forabdominal aorta conditions. However, the anatomy of the vasculaturebehind the eye is typically smaller, includes more branches, andincludes more sharp angles in the blood flow pathway. Further, thevascular system supplying blood to the eye is closer to the brain; anyuncaptured or non-rerouted debris may cause an immediate stroke.

The use of catheter delivery systems for positioning and deployingtherapeutic devices, such as balloons, stents, and embolic devices, inthe vasculature of the human body has become a standard procedure fortreating endovascular diseases. It has been found that such devices areparticularly useful as an alternative in treating areas wheretraditional operational procedures are impossible or pose a great riskto the patient. Some of the advantages of catheter delivery systems arethat they provide methods for treating blood vessels by an approach thathas been found to reduce the risk of trauma to the surrounding tissue,and they also allow for treatment of blood vessels that in the pastwould have been considered inoperable.

The present disclosure describes an apparatus, system, and method oftreatment of eye disease using any apparatus or system that involvesreverse blood flow or retrograde blood flow. More specifically, thepresent disclosure also describes apparatus, systems, and methods forinducing reverse blood flow or retrograde blood flow in one or morearteries, including, but not limited to, the OA.

In some embodiments of the present disclosure, retrograde blood flow maybe established between an artery and a vein. In other embodiments, areverse flow or retrograde system may be established in any locationsuitable for treatment of eye disease. Exemplary locations include, butare not limited to, the ICA, the external carotid artery (ECA), the CCA,the SOA, the STA, the OA, and an appropriate site in the venous system,which includes, but is not limited to, the IJV or the femoral vein.

In other embodiments, retrograde flow is used in combination with othermedical procedures and devices to access, treat, and/or deploy a medicaldevice in the fluid flow path between the ICA and the eye. As usedherein, fluid flow path refers to a section of the ICA, the ostium, theOA, and other arteries that supply blood to the eye.

A reverse flow system may be variously configured and include a widenumber of elements and devices. The typical reverse flow system includesan access device or port into an artery, an access device or port into avein, one or more tubes or conduits connecting the two access ports, andan occlusion device (e.g., balloon or clamp or the like).

Exemplary reverse and/or retrograde blood flow devices and systemsinclude, but are not limited to, U.S. Pat. Nos. 9,259,215; 9,241,699;9,265,512; 8,545,432; 7,927,347; 7,235,095; 6,936,060; 6,929,634;6,908,474; 6,905,490; 6,902,540; 6,855,162; 6,827,726; 6,824,558;6,645,222; 6,641,573; 6,540,712; 6,423,032; 6,413,235; 6,344,054;6,336,933; 6,302,908; 5,820,595; 5,709,701; and U.S. Patent ApplicationNos. 2009/0024072 and 2011/0160762; all of which are incorporated byreference herein in their entireties.

In some embodiments of the present disclosure, eye disease may betreated using at least one arterial access device and a retrograde flowsystem, using a percutaneous transfemoral approach, a transcervicalapproach, cervical access, or combinations thereof. The otherembodiments, the arterial access device and retrograde flow system mayuse a femoral or cervical approach.

In order to reverse blood flow in the CCA during interventionalprocedures, creation of a circuit is necessary to extract blood from theCCA and return it to a venous location. Extracting blood from the CCAand returning it to a venous location takes advantage of compensatoryblood flow through the circle of Willis (COW), high pressure of thearterial system, and low pressure of the venous system. Reversing bloodflow allows for filtration of the blood so that particulates generatedduring an interventional procedure are removed from circulation therebypreventing/reducing the possibility of an embolic event. Severalstructures are typically required to create the reverse blood flowcircuit: 1) an artery sheath which provides access to the artery; 2) anarterial occlusion device, typically catheter based, which is insertedinto the artery via the sheath. In some examples of the presentdisclosure, the device may incorporate a distal inflatable element,typically similar in design to an angioplasty balloon, which is designedto be positioned into the artery and inflated. The balloon isdimensionally designed to occlude the artery such that normal antegradeblood flow will be stopped upon full inflation and forced through one ofthe device lumens during the reverse flow portion of the procedure. Inother embodiments of the present disclosure, the device may have one ormore thru lumens capable of carrying blood and inserting medicalinstruments as well as a port (stopcock) for accessing these lumens andconnecting to a venous entry for returning the blood. 3) A venoussheath. This sheath provides access to the venous system and may includea port (stopcock) for connecting to the circuit to serve as the returnpoint for the arterial blood. 4) A blood filter. This filter is designedwith micropores that filter out particulate, but allow blood to flowfrom one side to the other. This filter may have lure connecters on eachend to allow for connection to the reverse flow circuit. 5) IV lines.These lines connect the occlusion device port (stopcock) to the filterand the filter to the venous sheath port (stopcock).

The present disclosure includes methods that may include, but are notlimited to, inserting and/or delivering an arterial access device to adesired artery and position, blocking flow in the artery, and allowingretrograde or reverse flow to cause blood to flow in a reverse orretrograde flow direction and into a shunt. The retrograde blood flowmay then be directed through the venous return device into a vein.

Some embodiments may include high flow capacity, one aspect of which maybe a delivery apparatus having a large bore. In other embodiments, thelarge bore may include a large internal dimension, useful for example,in delivering and using certain transcatheter devices.

In some examples of the present disclosure, lumen size for the system(circuit) components (including catheters, sheaths, stopcocks, andfilters) may be optimized for a particular location and/or circuit.Average CCA diameters can be in the 6.0 mm/18 Fr (or larger) range andaverage IJV diameters can be in the 13 mm/34 Fr (or larger) range.Larger than 2.66 mm/Fr 8 may also be used to accommodate theseartery/vein sizes.

Without intending to be bound by theory, it is believed that pore sizeof one or more filters may be optimized and/or coordinated in order toachieve medically appropriate filtration. In accordance with someembodiments of the present disclosure, the system may include one ormore filters. In systems having more than one filter, the pore size ofthe filters may be the same or different.

According to some embodiments of the present disclosure, the circuit maybe optimized for length. Without intending to be bound by theory, it isbelieved that carotid access may be beneficial, in part because of acircuit in which the guidewire may be approximately 15 inches in length.

In some embodiments of the present disclosure, the reverse flow systemis used to access or treat an arterial area or segment between the ICAand the eye. Such treatment includes, but is not limited to, removing ablockage. In some embodiments, the treatment may include restoring orincreasing blood flow to the eye. In other embodiments, the treatment,apparatus, or system, removes a blockage or constriction in the OA nearthe ICA, e.g., in the ostium and/or in the first section of the OAbefore the sharp bend in the artery.

Restoring and/or increasing blood flow is used herein to refer to anydevice, method, therapy, or combination that changes the blood flow tothe eye. Examples of such include, but are not limited to, increasingthe blood flow anywhere in the vasculature leading to the eye or aportion of the eye; removing or opening an obstruction in the fluid flowpath in the vasculature leading to the eye, e.g., from the ICA throughthe OA; delivering and deploying a stent in the fluid flow path in thevasculature leading to the eye; using atherectomy or similar devices tophysically remove portions of any obstructions in the vasculatureleading to the eye or portion of the eye; and localized drug and/or anoxygen device for increasing flow or amount of oxygen in one or more eyetissues. In some embodiments of the present disclosure, the device ormethod may be combined with a known or new drug or oxygen device inorder to treat one or more eye diseases or conditions.

The present disclosure also includes restoring and/or increasing theamount of nutrients that is available to one or more parts of the eye orto the eye area, specifically by removing or partially opening ablockage in one or more of the arteries that supplies blood flow to theeye. In some embodiments of the disclosure, a blockage is removed oropened in the ICA, the OA, the ostium (as used herein, referring to thejunction between the ICA and the OA), or combinations thereof. To ornear the eye, as used herein, refers to the vasculature system thatsupplies blood to the various structures of the eye. As noted above,nutrients as used herein include but are not limited to oxygen,hemoglobin, complement, and glucose.

The present disclosure also includes methods, devices, and systems forremoving a blockage in the ostium or a proximal segment of the OA nearthe ICA. In these embodiments, removing the blockage comprises opening achannel or access through the ostium sufficient to provide atherapeutically beneficial result to the eye, the rear of the eye, orportions thereof. The present disclosure also includes restoring and/orimproving blood flow anywhere in the vascular pathway to or within theeye.

The present disclosure should not be limited solely to changing vascularflow in order to improve or restore the amount of nutrients that aredelivered to the eye. For example, in some embodiments, the vascularflow may be unaffected for the most part, but the amount orconcentration of nutrients may be increased, thereby increasing theamount of nutrients that may be delivered to the eye or associated withthe eye. One skilled in the art may recognize, with the teaching of thisdisclosure, that there are other biological systems or capabilities thatmay be used to increase the amount of nutrients that are delivered tothe eye.

In other embodiments of the disclosure, reducing blockage includes, butis not limited to, piercing or penetrating the blockage. In otherembodiments, piercing and penetrating the blockage refers to obtainingsufficient blood and/or fluid flow through or around the blockedvascular area sufficient to provide a therapeutically beneficial amountof oxygen to the eye or a portion of the eye.

Some embodiments of the present disclosure include a retrograde flowsystem that does not require the use of a balloon or the like. In theseballoonless systems, methods, and assemblies, the flow direction elementmay be an external force applied to an artery to compress the arteryaround the sheath. As used herein, external force refers to any elementor structure that functions to apply force, to clamp or close the arteryagainst the sheath. Exemplary elements include, but are not limited to aclamp, vise, band, suture, pincer, contractor, constrictor, and thelike. In function, any such element compresses or closes the arteryagainst the sheath or tube, thereby forcing any blood flow through thelumen of the tube rather than around the tube.

The present disclosure includes methods and devices for treating anon-human animal. Some embodiments include treating a dog, including,but not limited to, treating central serous retinopathy.

In accordance with the present disclosure, a reverse flow system may bevariously configured and include a variety of elements and components.Typical components and elements include, but are not limited to, anarterial access device; a venous return device; one or more shunts; aflow control assembly; an arterial port; a venous port; a shunt valve; aflush line; one or more shut off valves; one or more connectors; one ormore tubing members; one or more syringes; one or more vessel closuredevices; one or more suture delivery devices; one or more interventionalcatheters; one or more interventional delivery devices; one or moreexternal receptacles; one or more adapters; one or more Y connectors; aflow state indicator; a flow rate activator; one or more sensors; atimer; contrast; one or more stopcocks; or one or more manifolds.

The present disclosure also includes a delivery system configured oradapted to position and/or orient a medical device in the OA;atherectomy or angioplasty in the OA; all in combination with a reverseflow system.

Referring to FIG. 1, according to an embodiment of the presentdisclosure, the retrograde flow system 100 can include the arterialaccess device 110, venous return device 115, and shunt 120 whichprovides a passageway for retrograde flow from the arterial accessdevice 110 to the venous return device 115. The system 100 may alsoinclude the flow control assembly 125, which interacts with the shunt120 to regulate and/or monitor retrograde blood flow through the shunt120.

FIG. 1 shows an exemplary embodiment of a retrograde flow system 100that is adapted to establish and facilitate retrograde or reverse flowblood circulation in the OA in order to limit or prevent the release ofemboli into the eye. The system 100 interacts with the OA to provideretrograde flow from the vasculature of the eye to a venous return site,such as the IJV (or to another return site such as another large vein oran external receptacle in alternate embodiments). The retrograde flowsystem 100 may include an arterial access device 110, a venous returndevice 115, and a shunt 120 that provides a passageway for retrogradeflow from the arterial access device 110 to the venous return device115.

An optional flow control assembly 125 can interact with the shunt 120.The flow control assembly 125 can be adapted to regulate and/or monitorthe retrograde flow from the OA to the IJV. Optionally, the flow controlassembly can be replaced with or used in conjunction with an in-linefilter. The flow control assembly 125 can interact with the flow pathwaythrough the shunt 120, either external to the flow path, inside the flowpath, or both.

The illustrated embodiment shows occluding the CCA. In anotherembodiment, the occlusion element is positioned in and occludes the ICAand/or the OA.

In an embodiment of the present disclosure, the arterial access device110 at least partially inserts into the ICA and/or the OA and the venousreturn device 115 at least partially inserts into a venous return sitesuch as the IJV. The arterial access device 110 and the venous returndevice 115 couple to the shunt 120 at connection locations 127 a and 127b. When flow through the ICA is blocked, the natural pressure gradientbetween the ICA and the venous system can cause blood to flow in aretrograde or reverse direction from the eye vasculature through the OAand the ICA, and through the shunt 120 into the venous system. The flowcontrol assembly 125 can modulate, augment, assist, monitor, and/orotherwise regulate the retrograde blood flow.

In an alternative embodiment, the flow control assembly may be replacedwith an inline blood filter; or the flow control assembly may be used incombination with an inline blood filter.

In the exemplary embodiment of FIG. 1, the arterial access device 110can access the CCA via a transcervical approach. Transcervical accessprovides a short length and non-tortuous pathway from the vascularaccess point to the target treatment site thereby easing the time anddifficulty of the procedure, compared for example to a transfemoralapproach. Additionally, this access route reduces the risk of emboligeneration from navigation of diseased, angulated, or tortuous ICA or OAanatomy. At least a portion of the venous return device 115 can beplaced in the IJV. In another embodiment, transcervical access to the OAis achieved percutaneously via an incision or puncture in the skinthrough which the arterial access device 110 is inserted. An occlusionelement 129, such as an expandable balloon, can be used to occlude theICA or OA at a location proximal of the distal end of the arterialaccess device 110. The occlusion element 129 can be located on thearterial access device 110 or it can be located on a separate device. Inan alternate embodiment, the arterial access device 110 accesses the ICAand the OA via a direct surgical transcervical approach. In the surgicalapproach, the OA can be occluded using a tourniquet 2105. The tourniquet2105 is shown in phantom to indicate that it is a device that is used inthe optional surgical approach.

Some embodiments of the present disclosure include an arterial accessdevice adapted and configured for use only with an interventionalreverse flow system. In these embodiments, there is no need for avascular surgeon or cut-down procedure. In devices, methods, and systemsaccording to this embodiment, a neuroradiologist or interventionalist isrequired to perform the procedure.

In another embodiment of the present disclosure, an example of which isshown in FIG. 2, the arterial access device or system 111 includes adevice delivery system 115, which may include an occlusion element 129,such as a balloon or expandable member, to block the blood flow; aconduit 112 or catheter having a lumen through which retrograde bloodmay pass; and a guidewire 114. The access device or system 111 may alsoinclude a sheath 113 having a distal end 116 configured to be flush withthe internal wall of the artery and located in a position near but abovethe occlusion element 129.

In the illustrated embodiment, the sheath accesses the artery through askin puncture in the neck (not a surgical cut-down), and the catheteraccesses the artery through a cut-down procedure. In another embodiment,the sheath accesses the artery through a skin stick in the neck and theinterventional catheter accesses the artery through a femoral access inthe groin.

In other embodiments of the arterial access device, the sheath isadapted to be introduced through an incision or puncture in a wall of aCCA, either an open surgical incision or a percutaneous punctureestablished, for example, using the Seldinger technique. The length ofthe sheath may be in the range of from 5 cm to 15 cm, or from 10 cm to12 cm. The inner diameter may be in the range of from 7 Fr (1 Fr=0.33mm) to 10 Fr, or 8 Fr.

The illustrated embodiment shows reverse flow through the catheter.Alternatively, reverse blood flow may pass through the sheath. Inanother embodiment, reverse flow can occur through either the sheath orthe catheter, and procedure devices can pass through whichever of thesheath or catheter that is not being used for reverse flow.

This configuration provides many advantages and alternatives. Reverseflow can pass through the conduit, the sheath, or both. The conduit maybe connected to a shunt, receptacle bag, or vein (e.g., IJV or femoralvein). The catheter comprising conduit 112 may be used without impingingthe function of the sheath, and vice-versa. As noted above, a vascularsurgeon is not required. Also this access device configuration issuitable for use with a cervical (carotid) or femoral access. In anotherembodiment, access is cervical, primarily because such a location savesapproximately ten minutes procedure time over femoral access, thusreducing the patient time in surgery and decreasing the amount of timethe patient is subject to stroke risk.

The arterial access device can have various features particularly usefulin a retrograde blood flow system. As shown in FIG. 1, the arterialaccess device 110 can include a flow lines 615 and 915 and a Y-adaptorto connect the sheath to a retrograde flow system. Optionally, thedistal sheath may include an occlusion element 129 for occluding flowthrough, for example the CCA. If the occluding element 129 is aninflatable structure such as a balloon or the like, the sheath caninclude an inflation lumen that communicates with the occlusion element129. The occlusion element 129 can be an inflatable balloon, but it canalso be an inflatable cuff, a conical, or other circumferential elementwhich flares outwardly to engage the interior wall of the carotid arteryto block flow, a membrane-covered braid, a slotted tube that radiallyenlarges when axially compressed, or similar structure which can bedeployed by mechanical means, or the like. In the case of balloonocclusion, the balloon can be compliant, non-compliant, and elastomeric;reinforced; or have a variety of other characteristics. In anembodiment, the balloon is an elastomeric balloon which is closelyreceived over the exterior of the distal end of the sheath prior toinflation. When inflated, the elastomeric balloon can expand and conformto the inner wall of the carotid artery. In an example of the presentdisclosure, the elastomeric balloon is able to expand to a diameter atleast twice that of the non-deployed configuration, frequently beingable to be deployed to a diameter at least three times that of theun-deployed configuration, at least four times that of the un-deployedconfiguration, or larger.

In some embodiments of the present disclosure, the arterial accessdevice may include a catheter having a backstop; a balloon, typicallyattached to a central guidewire; and a knot or the like (some othergeometrically shaped element) extending on the guidewire outwardly anddistally from the balloon. In use, the knot may be deployed in theregion of the plaque or obstruction, and the knot may be used to loosenparticles in the artery, which flow back toward the backstop and/or thecatheter. The balloon may then be partially deployed, whereby particlesmay become trapped between the balloon and the end of the catheter (orbackstop). The balloon may then be drawn back into the catheter, therebydrawing and capturing particles within the lumen of the catheter. Thecatheter, carrying the particles, may then be pulled out of the body.

Alternative elements or structures of the system described in thepresent disclosure may include a guidewire with a distal tip comprisinga kite tail shaped element; a backstop comprising a funnel shaped cage;and a balloon that is deployed and/or expanded in stages, e.g., theproximal end first, thereby forcing, pushing, or capturing particlesinto the backstop.

The system 100 is adapted to regulate retrograde flow in a variety ofmanners. Any combination of the pump, valve, syringe, and/or variableresistance component can be manually controlled by the user orautomatically controlled via a controller to adjust the retrograde flowrate. Thus, the system 100 can regulate retrograde flow in variousmanners, including controlling an active flow component (e.g., pump,syringe, etc.), reducing the flow restriction, switching to anaspiration source (such as a pre-set Vaculok syringe, Vacutainer,suction system, or the like), or any combination thereof.

Methods of Use

In an exemplary method of the present disclosure, the distal sheath ofthe arterial access device 110 is introduced into a carotid artery andinto the ICA. As noted above, entry into the carotid artery can be via atranscervical or transfemoral approach, or any approach suitable forintroducing a distal portion of a catheter into the OA. After the sheathof the arterial access device 110 has been introduced into the ICA, theblood flow will continue in an antegrade direction with flow from the OAentering both the ICA and the ECA.

The venous return device 115 can then be inserted into a venous returnsite, such as the IJV. The shunt 120 can be used to connect the flowlines 615 and 915 of the arterial access device 110 and the venousreturn device 115, respectively (as shown in FIG. 1). In this manner,the shunt 120 provides a passageway for retrograde flow from the atrialaccess device 110 to the venous return device 115. In anotherembodiment, the shunt 120 can connect to an external receptacle ratherthan to the venous return device 115.

Once all components of the system are in place and connected, flowthrough a carotid artery, ICA, or OA can be stopped, such as by usingthe occlusion element 129 as shown in FIG. 1. The occlusion element 129can be expanded at a location proximal to the distal opening of thesheath to occlude the OA. Alternately, the tourniquet 2105 or otherexternal vessel occlusion device can be used to occlude the OA to stopflow. In an alternative embodiment, the occlusion element 129 can beintroduced on second occlusion device 112 separate from the distalsheath 605 of the arterial access device 110. The OA can also beoccluded with a separate occlusion element, either on the same device110 or on a separate occlusion device.

At that point, retrograde flow from the OA and ICA can begin and canflow through the sheath, the flow line 615, the shunt 120, and into thevenous return device 115 via the flow line 915. The flow controlassembly 125 can regulate the retrograde flow as described above. Whilethe retrograde flow is maintained, a stent delivery catheter can beintroduced into the sheath. The delivery catheter can be introduced intothe sheath through a hemostasis valve and the proximal extension of thearterial access device 110. The delivery catheter can be advanced intothe ICA and the OA.

Vibrating Guidewire

Some embodiments of the present disclosure may include a conventionalguidewire. For example, a guidewire with a basket or the like on thedistal end, or a guidewire having a geometrically shaped element on thedistal end.

This guidewire is intended for neuro interventional procedures in whicha reverse flow system is in use. The guidewire is designed to be used incervical access where there is a need to remove plaque from a specificarterial segment. Once reverse flow is established, the guidewire isplaced in the location of the stenosis and a vibration is induced via anelectric motor. This vibration may loosen material either due to directcontact with general vibration, or with contact and by use of a specificresonance frequency of the target material for removal. The guidewire isof general design, however it is optimized for cervical accessprocedures and is designed to fit within the vibratory motor housing insuch a way as to contact the motor. Contact with this motor imparts avibration in the guidewire which is transmitted to the target anatomyand serves to aid in the removal of plaque.

In some embodiments, the vibratory motor is positioned on and orattached to a surgical drape. It is intended that the vibratory motorshould remain substantially stationary. The guidewire passes through oris attached to the vibratory motor. Positioning in the target anatomy isaccomplished by moving the guidewire in and out of the arterial segmentbeing treated.

Vibrating Angioplasty Balloon

The present disclosure includes a balloon, which may be a conventionalballoon or may include geometric features intended to facilitateplaque/obstruction removal or dislodgement. Balloons may be of any of avariety of shapes (asymmetrical, spiral, etc.) and/or coated withmaterials for facilitating plaque removal (abrasives, etc.).

This balloon is intended for neuro interventional procedures in which areverse flow system is in use. The balloon is designed to be used incervical access where there is a need to remove plaque from a specificarterial segment. Once reverse flow is established, the balloon isplaced in the location of the stenosis and a vibration is induced via anelectric motor. This vibration may loosen material either due to directcontact with general vibration, or with contact and by use of a specificresonance frequency of the target material for removal. The balloon isof general design, however it is optimized for cervical accessprocedures and is designed to fit within the vibratory motor housing insuch a way as to contact the motor. Contact with this motor imparts avibration in the balloon which is transmitted to the target anatomy andserves to aid in the removal of plaque.

In accordance with the present disclosure, the vibratory balloon, and/orthe vibratory guidewire may loosen plaque or an obstruction, andplaque/obstruction particles and the like may be removed from the siteusing the reverse flow system.

In another embodiment, a medical device or agent is capable ofdelivering drugs to the ostium for the purpose of improving vascularblood flow at the ostium and within the OA. Exemplary drugs include, butare not limited to, low dose Viagra (or equivalent PDE 5 inhibitor),Lucentis, Avastin, Taxol, Rapamyacin, or other pharmaceuticals used toimprove vascular blood flow.

FIGS. 3A and 3B illustrate exemplary anatomy relating to an eye of apatient or subject. The vasculature in the fluid flow path to and fromthe eye, the rear of the eye, portions of the eye, or regions near theeye, includes, among other arteries and veins, the ICA 12, the OA 14,and the junction 16 between the ICA 12 and the OA 14, which is alsoreferred to as the ostium, as shown in FIG. 3A. In most patients, OA 14extends at an acute angle relative to ICA 12, as shown in FIGS. 5 and 6.In some patients, a flap of tissue (not shown) may extend between OA 14and ICA 12. That is, in some arrangements, the flap of tissue may bepositioned in junction 16. Additional areas of the anatomy, as shown inFIG. 3B, may include the vascular system which is commonly referred toas the terminal branches. These areas include, but are not limited to,the SOA, the STA, the DNA, and the FA.

Diseases and conditions of the eye (e.g., AMD, glaucoma, diabeticretinopathy etc.) may result in decreased blood flow to and around theeye, which is believed to contribute to nutrient (e.g., oxygen)depletion in and around the eye. Without being bound by theory, it isbelieved that conditions that lead to lowered oxygen (or other nutrient)delivery to the tissue in and around the eye mediates and/or causes anyof a variety of eye diseases, include, but are not limited to, AMD.Possible conditions include, but are not limited to, one or more of thefollowing: blockage(s) in ICA 12; blockage(s) in OA 14; reduced bloodflow anywhere in the fluid flow path between ICA 12 and eye tissue;reduced blood flow rate anywhere in the fluid flow path between ICA 12and eye tissue; decreased hemoglobin amount or delivery to one or moreeye tissues; and blockage(s) or reduced flow in any of the junctions orostia between any of the vasculature between the ICA 12 and one or moreeye tissues (e.g., junction 16).

According to aspects of the present disclosure, diseases and conditionsof the eye may be directly mediated by improved blood flow to thevasculature of the eye (e.g., the posterior of the eye). For example,the systems, devices, and methods described herein may restore orincrease the amount of oxygen (or other nutrient) that reaches the eyeor an eye area which may include removing or opening a blockage (orpartial blockage) in one or more vascular systems that support the eye.Opening a blockage or partial blockage may include increasing orrestoring blood flow to or around the eye. Increasing blood flow mayinclude, but is not limited to, increasing the blood flow rate. That is,aspects of the present disclosure may be directed to one or moreintravascular medical devices and/or methods intended or configured tosufficiently unblock or at least partially restore blood flow in ablocked or partially blocked artery such that nutrient (e.g., oxygen)content is increased distal to the blockage. For example, in someaspects, the present disclosure is directed to devices and methods forrestoring blood flow through the ostium or junction 16.

In additional aspects, the disclosure is directed to using such devicesand methods to restore or increase blood flow and/or or restore orincrease nutrient (e.g., oxygen) levels, to the eye or a portionthereof. Restoring or increasing oxygen flow may include using thedevices and methods described herein, or equivalent devices and methods,but is not to be limited thereby. Various conditions or diseases of theeye may be treated according to embodiments of the disclosure. Exemplaryconditions and diseases are described in U.S. Provisional PatentApplication No. 62/396,091, entitled “Systems and Methods for TreatingEye Diseases Using Retrograde Blood Flow,” filed Sep. 16, 2016, andincorporated by reference herein in its entirety.

Exemplary embodiments of the present disclosure provide a reverse flowor retrograde flow device and system for the treatment of an eye,including the treatment of any diseases or conditions of the eye. Such areverse or retrograde flow may protect the brain or the eye from thepossibility of an embolic event or other damage during a cerebralinterventional procedure.

In exemplary embodiments of the present disclosure, the resistance ofblood flow through the system from the arterial side to the venous sidemay be reduced by a cervical approach. In some arrangements, one or moredevices or sheaths may be inserted through the skin of a face of asubject. In certain embodiments of reverse flow systems, as will bedescribed below, tubing, stopcocks, hemostasis valves, andblood/particulate filters with large lumens and/or high flow throughputmay be used. In some embodiments, the device may be about 8.5 French(2.83 mm) to about 9.0 French (3 mm). In addition, the length of thetubing may be minimized, which when combined with larger luminaldiameters and high flow blood/particulate filters, may result inreducing resistance to blood flow through the system from the arterialside to the venous side. Certain embodiments, as also described below,include a dedicated circuit to provide for reverse blood flow in the OAduring the reverse flow procedure.

As will be discussed below in connection with the figures, a reverseflow system according to an exemplary embodiment may include some or allof the following components: two percutaneous sheaths (including a firstarterial sheath and a second venous sheath); intravenous tubing with alow flow resistance blood/particulate filter and connecting the sheathsbetween the arterial and venous sheath access points; two stopcocks, afirst stopcock containing a hemostasis valve on the arterial side of theblood filter near the arterial sheath; and a third sheath inserted intoone of the terminal branches of the OA, and connected via a hemostasisvalve to the intravenous tubing. The tubing is connected to a port ofthe stopcock attached to the arterial sheath. This exemplary arrangementrepresents a separate circuit which takes blood from the arterial sheathand feeds it into a terminal branch of the OA thereby inducing reverseflow in the OA. Additional components may include, on the venous side ofthe blood filter, a single stopcock. The stopcocks may be designed tomaximize the luminal diameter such that resistance to blood flow fromthe arterial side to venous side of the system is minimized. Minimizingthe blood flow resistance of the system will maximize the speed andability of the system to remove potential embolic material from theartery under reverse flow and return arterial blood to the venoussystem.

In one exemplary embodiment shown in FIG. 4, a flow reversal system 70includes: (i) an arterial sheath 20 having proximal and distal ends witha lumen extending therethrough; (ii) a venous sheath 30 having proximaland distal ends with a lumen extending therethrough; (iii) an expandableoccluder 60 at the distal end of arterial sheath 20; (iv) a venousreturn circuit 21 at or near a distal end of sheath 20 proximal toexpandable occluder 60; (v) a conduit 40, with a particulate/bloodfilter 45 interspersed, fluidly connecting a proximal opening ofarterial sheath 20 to the venous sheath 30; and (vi) a circuit 50connecting an arterial sheath stopcock 22 with a terminal branch of OA14 (while the STA is depicted in FIG. 4, any other terminalbranch/vessel downstream from OA 14 may be used) via a sheath 52.Arterial sheath 20 is placed in the CCA, though it could be placed inICA 12, and the venous sheath is placed in the IJV, though other venousvessels may be used. A pressure gradient is created so that blood flowsinto the distal opening of arterial sheath 20, through conduit 40, andexits through a return port into the venous sheath 30. Flow reversalsystem 70 may be cervically-placed. Additionally, as shown in FIG. 4,arterial sheath 22 may further include an additional stopcock 23, venoussheath 30 may include a venous stopcock 31, and sheath 52 may include astopcock 51.

An additional connection to the arterial sheath 20 includes circuit 50that connects to sheath 52 placed in a terminal artery of OA 14 suchthat a portion of blood flow from the arterial sheath 20 is sent throughcircuit 50 and into the terminal artery of OA 14 for the purpose ofreversing flow in OA 14, other arteries, and/or other arteries thatsupply blood to the eye.

Without intending to be bound by theory, it is believed that blockingthe flow of blood facilitates the reversal of blood flow across atreatment site. In an example of the present disclosure, expandingexpandable occluder 60 in the CCA blocks the flow through the CCA andcauses the pressure on the downstream side, e.g., distal side ofexpandable occluder 60, to drop, thereby facilitating blood fromcontralateral vessels to flow toward the lower pressure and flow intoarterial sheath 20, which carries embolic debris into theblood/particulate filter 45.

In embodiments of the present disclosure, the expandable occluder 60 canbe any shape which occludes a radial space about the distal region orend of the arterial sheath 20, so as to ensure blood and emboli isdirected into the distal opening of the arterial sheath 20, rather thanbecoming trapped between an intraluminal wall of the blood vessel and anouter wall of arterial sheath 20. For example, expandable occluder 60can be disc-shaped, donut-shaped, cylindrical, cone-shaped,funnel-shaped, or any other shape that substantially occludes the flowof blood about the radial space of the distal region of the arterialsheath 20 and defines the outer wall of the arterial sheath 20 to permitblood to pass through the distal opening of the arterial sheath 20. FIG.5 shows an exemplary cross section of the placement and structure of aflow direction balloon 60′ in the ICA 12, which is an alternative toplacement in the CCA. As shown, flow direction balloon 60′ may include atapered cylinder or cone shaped balloon having a proximal end coupled toa distal end of arterial sheath 20 and may guide or otherwise facilitatea flow of blood through arterial sheath 20. That is, a wall or surfaceof balloon 60′ may narrow towards a distal end of arterial sheath 20,and contact a wall of ICA 12 at distal portions of balloon 60′.

Embodiments of the present disclosure also include a retrograde flowsystem that does not require the use of a balloon or the like. In thesesystems, methods, and assemblies, the flow direction element applies anexternal force applied to an artery to compress the artery around thesheath 20. Such an embodiment is shown in FIG. 6, where the externalforce is provided by a clamp 62.

Embodiments of the present disclosure include any tool or device thatfunctions to apply force, to clamp, or to close the artery againstsheath 20. Exemplary elements include, but are not limited to, a clamp,a vise, a band, a suture, a pincer, a contractor, a constrictor, and thelike. Any such element compresses or closes the artery against thesheath 20, thereby forcing any blood flow through the lumen of thesheath 20 rather than around the sheath 20.

In other embodiments of the present disclosure, the flow directionelement of the system is used to initiate the reversal of flow in theCCA (or the ICA 12). For example, flow reversal may be accomplished byuse of an expandable occluder 60, such as an inflatable balloon device,e.g., balloon 60′. In another example, flow reversal may also beaccomplished without a balloon by using a sheath that has external forceapplied to compress the CCA/ICA 12 against the tube portion of thearterial sheath 20. This compressive action serves to prevent blood flowaround the arterial sheath 20 (in the same way as an inflatable balloondoes from inside the CCA/ICA 12) and force blood through the arterialsheath 20 and into the venous circuit of the system, thereby providingflow reversal. The sheath may be of conventional design, or may containelements that facilitate compressing the CCA/ICA against the arterialsheath 20 for the purpose of establishing flow reversal. These elementsmay include the following: (1) specific arterial sheath 20 durometermaterial design to accommodate compressive force while maintainingarterial sheath 20 lumen integrity; (2) radiopacity elementsincorporated into the arterial sheath 20 to allow for confirmation ofproper clamping position via fluoroscopy; and/or (3) incorporation of adistal sheath inflatable element (e.g., expandable occluder 60 and/orballoon 60′) to aid in the direction of blood flow into the arterialsheath 20 lumen and to prevent blood leakage between the arterial sheath20 and the CCA/ICA 12 during clamping.

In another embodiment of the present disclosure, the arterial accessdevice may include a catheter or sheath 20 having a backstop (e.g.,balloon 60′); and a central guidewire (not shown) for passing through alumen of the sheath 20. The guidewire includes an attached inflatableballoon, and a knot, brush, or other geometrically shapedartherectomy-like element extending outwardly on the guidewire, distallyof the balloon. In use, the element may be deployed in the region of aplaque or obstruction to loosen particles in the artery, which flow backtoward sheath 20. The guidewire balloon may then be partiallyinflated/deployed, whereby particles may become trapped between theballoon and the end of the sheath 20 and balloon 60′. The guidewireballoon then may be drawn back into the sheath 20, thereby drawing andcapturing particles within the lumen of the sheath 20. The sheath 20,carrying the particles, then may be pulled out of the body and/or theparticles may be aspirated out of sheath 20.

Other embodiments of the present disclosure may include a guidewire witha distal tip comprising a kite tail shaped element; a backstopcomprising a funnel shaped cage; and/or a balloon that is deployedand/or expanded in stages, e.g., the proximal end first, therebyforcing, pushing, or capturing particles into the backstop. Additionalinterventional procedures and devices are described below and in U.S.Provisional Patent Application No. 62/396,091, entitled “Systems andMethods for Treating Eye Diseases Using Retrograde Blood Flow,” filedSep. 16, 2016, and International Application PCT/US2017/021673, entitled“Systems and Methods for Treating Eye Diseases Using Retrograde BloodFlow,” filed Mar. 9, 2017, both of which are incorporated by referenceherein in their entireties.

As mentioned above, a purpose of reverse flow is to channel embolicdebris of a wide range of particle sizes away from particularly at-riskareas during an endovascular treatment. In an embodiment of the presentdisclosure, blood, along with embolic debris in some embodiments, fromthe treatment site is rerouted through a sheath/catheter to anotherlocation, for example from high to low pressure. A filter (e.g., filter45) can be included to capture embolic debris from the blood. Once theblood passes through the filter, the blood may be re-introduced into thevenous circulation.

Some embodiments of the present disclosure include methods of achievingreverse flow in cerebral vasculature, and, for example, in the OA 14 andICA 12. In some examples, prior to performing the method, a duplexultrasonography scan may be performed to measure the distance betweenthe planned puncture site and the carotid bifurcation and also toconfirm the anatomical status of the CCA.

To reverse blood flow, according to an embodiment of the presentdisclosure, the following steps may be taken:

1) A small 4 cm transverse incision is made at the base of the neckbetween the two heads of the sternocleidomastoid muscle. The CCA isdissected free for about two centimeters, as well as the IJV. A vesselloop is placed around either vessel.

2) A 9 French venous sheath, e.g., sheath 30, is inserted in the caudaldirection over a wire after puncturing the jugular vein.

3) An arterial sheath 20 is inserted in the CCA in a cephalad directionusing a guidewire. The arterial sheath 20 has a stopcock 22 attached tothe proximal end of the arterial sheath 20. The guidewire may be a stiff0.035″ guidewire introduced in the ECA under fluoroscopic.

4) An additional, appropriately sized arterial sheath (e.g., sheath 52)is inserted into a terminal artery of OA 14 and connected viaintravenous tubing (e.g., circuit 50) to the arterial sheath stopcock22.

5) The three-way-stopcock 22 is opened to allow the blood to fill thetubing or conduit 40 and the filter 45. The stopcock of the arterialline is opened and then, after flushing blood, is connected to thevenous tubing establishing the fistula.

6) The occluding element (e.g., balloon 60′) on the distal tip of thelarge lumen arterial sheath 20 is inflated in the CCA. At this moment,flow reversal is established, and the OA 14 sheath 52 stopcock 51 isopened to establish reverse flow in the OA 14 circuit. A small injectionof contrast media through the side-port of the arterial sheath willconfirm that flow is reversed.

According to this method, a temporary, reversible arterio-venous fistulacan be created between the CCA (or the ICA 12) and the jugular vein atthe base of the neck through, for example, a small incision done underlocal anesthesia. The fistula produces a temporary reversal of flow ofthe ICA 12 or the OA 14, which may itself unblock the OA 14, or while aninterventional procedure may be performed. This flow reversal allowsparticulate to be removed from the bloodstream during an interventionprocedure, to not pose a cerebral or eye embolic threat or damage.

After creating the fistula, the operator may commence an interventionalprocedure. The interventional procedure may include providing one ormore stents implanted in the vasculature supplying blood to the eye. Forexample, a stent may be placed in ICA 12, OA 14, or at the ostium orjunction 16 of ICA 12/OA 14. The stent may provide patency. The stentmay include radiopaque features to guide in accurate placement. Otherinterventional procedures may include use of a balloon in anangioplasty-like procedure, or performing an atherectomy. Theseprocedures may restore and/or increase the amount of oxygen (or othersuch nutrients) being delivered to the eye. Devices, methods, therapies,or combinations that change the oxygen (or other nutrient) content in ornear the eye include, but are not limited to, increasing the blood flowanywhere in the vasculature leading to the eye or a portion of the eye;removing or opening an obstruction in the fluid flow path in thevasculature leading to the eye; delivering and deploying a stent in thefluid flow path in the vasculature leading to the eye; using atherectomyor similar devices to physically remove portions of any obstructions inthe vasculature leading to the eye or portion of the eye; and localizeddrug and/or an oxygen device for increasing flow or amount of oxygen inone or more eye tissues. In some embodiments, a device or method of thepresent disclosure may be combined with a known or new drug or oxygendevice in order to treat one or more eye diseases or conditions. Thepresent disclosure provides for an apparatus for deployment of adetachable diagnostic or therapeutic implant device such as a stent,embolic coil, or other vascular occlusion device using a catheter,whereby placement of a stent or the like in a portion of the carotidartery changes the diameter of the ICA 12 and/or OA 14, which in turnincreases blood flow between the ICA 12 and the eye.

Exemplary interventional procedures, and implants, catheters,guidewires, balloons, and other therapeutic devices for use ininterventional procedures, according to embodiments of this disclosure,are described in the following documents, U.S. Provisional PatentApplication No. 62/396,091, entitled “Systems and Methods for TreatingEye Diseases Using Retrograde Blood Flow,” filed Sep. 16, 2016; and U.S.Patent Application No. 15,609,547, entitled “Devices and Methods forTreating Occlusion of the Ophthalmic Artery, filed May 31, 2017, both ofwhich are incorporated by reference herein in their entireties.

It is intended that this disclosure should not be limited by the type ofprocedure (cervical) or use of specific instruments necessary to providean interventional result. For example, in accordance with thisdisclosure, eye disease may be treated using at least one arterialaccess device, using a percutaneous transfemoral approach; atranscervical approach; cervical access; or combinations thereof.Exemplary access procedures and devices are described in U.S.Provisional Patent Application No. 62/396,091, entitled “Systems andMethods for Treating Eye Diseases Using Retrograde Blood Flow,” filedSep. 16, 2016, and incorporated by reference herein in its entirety.

In accordance with this disclosure, a reverse flow system may beestablished in any location suitable for treating an eye disease orcondition. These locations include, but are not limited to, the ICA 12,the ECA, the CCA, the SOA, the STA, the OA 14, and an appropriate sitein the venous system, including, but not limited to, the IJV or thefemoral vein.

The present disclosure also relates to medical devices and therapies fortreating occlusion of the OA, and specifically, to novel interventionaldevices for restoring and/or increasing vascular blood flow to the rearof the eye.

Without intending to be bound by theory, it is believed that the primarycausative effect for WAMD, glaucoma and diabetic retinopathy isocclusion of the OA such that normal blood flow is restricted (ischemia)to the rear of the eye. As a result of this ischemia, hypoxia (resultingin neovascularization) is induced in these structures and visioneventually devolves into a dysfunctional retina (WAMD). From this, thepresent disclosure describes possible devices that may be used toprovide a treatment methodology for WAMD, which may include a device(s)for performing interventional work in the OA and surrounding structuresto restore/increase vascular blood flow, and a device for selectivelyinducing retrograde blood flow in the retinal vasculature viamanipulation for 10P.

The present disclose includes an interventional device designed to gainaccess to and deliver direct mechanical and/or drug therapy to aspecific location of the anatomy. While the following examplesspecifically detail the necessary components for a particular OAapplication, this technology may be used in any anatomical location inwhich removal of material is desired in a luminal environment. Thisenvironment may be vascular or not and may be used in any tubal, luminalor other similar anatomical structure where removal of material isdesired. As such, some embodiments may be scaled, modified orconstructed such that it can provide therapy for a specific luminalanatomical location/need. In some embodiments, the interventional devicedesign may be based on a central wire, hypotube, coil, balloon orcombination thereof. In other embodiments, the interventional device maybe made of stainless, nitinol, polymer, other materials, or acombination thereof, and designed to accommodate specific approaches(carotid, subclavian, femoral, endoscopic or laparoscopic). For example,entrance into the body may be provided by a vascular access elementwhich may be typical, or may be designed specifically for use with adevice according to the present disclosure (e.g., catheter sheathintroducer or equivalent). The disclosed device fits within a sheath,which is designed to provide a protective element for the device as wellas to prevent vessel trauma during delivery to the target site. Thedistal portion includes the ability to provide distal protection in theOA, as well as an element to provide diametric interference. This areaof diametric interference is designed to interface with the targetvessel segment (e.g., lesion) such that specific and deliberatemanipulation provides for the ability to selectively remove materialfrom the lesion site. The diametric interference element also providesfor the ability to compress such that it fits within the device sheathto provide a minimal diametric dimension. This diametric portion is alsoreferred to as an interventional element. Once the device is placed atthe target anatomy, the interventional element is positioned such thatit is outside the sheath and it conformally fits the inner diameter ofthe target anatomy. The interventional element also contains a designelement that allows for tissue removal when manipulated in a specificmanner. That manner includes manual rotation, manual push/pull,mechanical rotation, mechanical push/pull, site specific drug deliveryor a combination of some or all of those. Additionally, the tissueremoval device and conforming element is optionally different devices,two devices or different segments of the same device. Once materialremoval is complete, the interventional element is pulled into thesheath, along with the distal protection portion (equipped) of thedevice and the entire assembly removed. It is also possible to removethe interventional element for cleaning and to replace and continue.Furthermore, this device may deliver drug therapy directly to the areaof intervention. For example, delivery of a pharmaceutical compound toreduce the rate of restenosis may be possible as well as a variety ofother pharmaceutical compounds. The device is also constructed such thatit is able to provide interventional therapy in the form of energydelivery. This includes, but is not limited to, laser, ultrasound,cryogenic, radiofrequency (RF), and/or other energies or combinationthereof. Additionally, there is also the provision for the ability toprovide direct optical viewing of the target site prior to, during, andafter administration of therapy. There is an ability to combine multipledrug therapies for a single condition or multiple conditions. Forexample, Sirolimus for antiproliferative effect post angioplasty. Inaddition to this or separate from this, a statin may be included andeluted as lipid-like deposits called drusen can be concomitant to WAMD.It is presumed that the slow elution of a statin would reduce the sizeand number of drusen deposits and thereby improve eyesight.

Interventional Device—Common Device Elements

1. Ability to visualize under fluoroscopy

2. internal carotid access (can be done via subclavian or femoral)

3. Distal protection element in the ICA

4. Distal protection element in the OA

5. Works in OA diameter ranges between 0.7 mm to 1.4 mm—derived byatmospheric pressure applied to the conformal element

6. Working length for OA estimated to be about 15 inches, furtherdefinitions included

7. Approaches other than ICA also included

8. Ability to remove material from the OA and transport out of thevasculature

9. Ability to induce retrograde flow, either continuously, or on demandfor specific time periods

10. May use a guiding catheter to cannulate the OA from the ICA(combination of GC features with sheath to have an ‘all in one’)

Interventional Device—Singular Elements (Specific to a ParticularDesign)

1. Distal OA protection as an integral element of the device

2. Distal OA protection as a separately placed/removed device

3. Distal CA protection as an integral element of the device

4. Distal CA protection as a separately placed/removed device

5. Distal ICA protection as a integral placed/removed device

6. Distal ICA protection as a separately placed/removed device

7. Ability to deliver an RF element for therapy

8. Ability to deliver a laser element for therapy

9. Ability to deliver an ultrasound element for therapy

10. Ability to deliver a cryogenic element for therapy

11. Ability to deliver drugs via infusion

12. Ability to deliver drugs via injection (e.g., bolus-tissueplasminogen activator (TPA))

13. Drug delivery capability before, during and after material removal

14. Ability to deliver drugs via micro needles

IA. Interventional Device—Specific Examples: Solid Corewire Based

FIGS. 7A and 7B show an embodiment of the present disclosure having anAspiration Core. The design is based on a solid metallic corewire withintegrated aspiration capability. The device consists of the followingelements and features as detailed in FIGS. 7A and 7B:

1. Center corewire

2. Longitudinal indentations

3. Delivery sheath

4. Cutting element

5. Distal protection element

6. Atraumatic tip

FIG. 7A depicts the device with the delivery sheath 3 covering thecutting 4 and distal protection 5 elements, which are both mounted onthe central core 1. The tip of the device contains an atraumatic tip 6to aid in placement of the device.

FIG. 7B depicts the delivery sheath pulled back and the cutting anddistal protection elements both in a deployed position. Aspiration isaccomplished by either flushing and aspirating using alternatelongitudinal channels 2 of the corewire, or by a combination use oflongitudinal channels and the delivery sheath, one for flushing and theother for aspiration. Once the procedure is complete, the device iswithdrawn back into the delivery sheath and positioned as seen in FIG.7A. The device is then safely withdrawn from the anatomy.

Generally, the overall length of the device is optimized for theanatomical location and approach. For example, for use within the OA, anoverall length of about 160 cm or about 15.00 inches for the devicewould be used in conjunction with an appropriately designed sheath. Themaximum overall diameter of the sheath would be about 1.0 mm range(after inflation), with the cutting and distal protection elementsoffering a conformal fit capability in the deployed range of between 0.7mm to 1.4 mm as dictated by the specific dimensions of the OA and thelesion site. These overall length and diametric dimensions would beadjusted based on the specific applications and is contemplated aswithin the scope of the present disclosure. In addition, the specificmaterial composition, formulation and manufacturing parameters ofmaterial used would be refined to address the specific application andis contemplated as within the scope of the present disclosure. Thisdimensional information applies to all of the designs disclosed. In oneexample, the lesion crossing profile of this device is less than 0.2 mm.A range of appropriate profile dimensions is contemplated as within thescope of the present disclosure.

A. Interventional Device—Specific Examples: Plain Core—Non AspirationCore

The design in FIG. 8 is based on a solid corewire and does not havespecific aspiration capability. The device consists of the followingelements and features:

1. Center corewire

3. Delivery sheath

4. Cutting element

5. Distal protection element

6. Atraumatic tip

This disclosed subject matter of FIG. 8 is essentially the same as theFIGS. 7A and 7B aspiration core with the exception that the core is notdesigned to facilitate aspiration. The remaining elements of the deviceare essentially similar to the aspiration core design. FIG. 8 depictsthe delivery sheath pulled back and the cutting and distal protectionelements both in a deployed position. Once the procedure is complete,the device is withdrawn back into the delivery sheath and positioned ina similar fashion as seen in the aspiration core FIG. 7A. The device isthen safely withdrawn from the anatomy.

It should also be noted that the corewire based design may includeelements that are much simpler in design than illustrated in the sketchabove. These designs could include a wire with a specific drawn profilethat is inserted into the anatomy such that movement of the wire wouldallow an interface between the profile of the corewire and the anatomyto facilitate lesion material removal. These particular designs couldinclude 1) a straight ‘as drawn’ wire, 2) an as drawn wire with a twistor 3) a selective combination of the two.

FIGS. 9A and 9B depict drawn wire with a twist and the distal tipsegment of our initial corewire based prototype design.

FIG. 10 depicts the initial corewire based prototype overallconfiguration.

B. Interventional Device—Hypotube Based

Integral elements—The design in FIGS. 11A-11C is based on a hollowmetallic tube. Aspiration capability is not detailed in this sketch, butmay be possible with the addition of a central flush source. The deviceconsists of the following elements and features as detailed in FIGS. 11Aand 11B:

1. Central Corewire Hypotube

3. Delivery sheath

4. Cutting element

5. Distal protection element

6. Abrasives

9. Guidewire

FIG. 11A depicts the device with the delivery sheath 3 covering thecutting 4 and distal protection 5 elements, which are both cut from theactual hypotube 1 and as such, are integral to the hypotube

An alternative version of this design would be a hypotube version withcutting and distal protection elements mounted on the hypotube. Therewould also be a provision for an element that would be positioned in thelumen after removal of the guidewire. This element would serve todeliver fluid for flushing. In this example, aspiration could beaccomplished by applying suction to the proximal hypotube such thatfluid is removed as well as debris while flushing is activated. Whilethese specific embodiments are not sketched, this disclosure describessuch configuration. A guidewire 9 extends down the inner lumen of thehypotube to provide a means for navigating the anatomy. Upon placementwithin the target anatomy, the guidewire is removed and the sheath ispulled back, deploying the cutting and distal protection elements.Deployment of the distal elements is controlled by selectivemanufacturing processes which preferentially ‘train’ the elements tobehave in a certain fashion such that they exhibit a condition known as‘shape memory.” This shape memory is exhibited by the hypotube when itis in an unrestrained position. Abrasives 6 mounted, coated, or integralwith the cutting element may be designed to facilitate material removaland shaping of the lesion.

FIG. 11B depicts the delivery sheath pulled back and the cutting anddistal protection elements both in a deployed position. Once theprocedure is complete, the device is withdrawn back into the deliverysheath and positioned as seen in FIG. 11A. The device can then be safelywithdrawn from the anatomy.

FIG. 11C depicts an alternative embodiment of the hypotube design. Inthis example, all elements are similar as in the previous sketch, withthe exception of number 7. Element number 7 details a moveable internalcorewire, which is joined with inner distal tip of the hypotube suchthat longitudinal movement of the corewire may serve to either expandelements 4 and 5, or compress them. When the procedure is complete,removal of this device would be accomplished in a similar fashion asdescribed in FIG. 11B as above.

IC. Interventional Device—Polymer Based Tube

FIG. 12A depicts the device with the delivery sheath 3 covering thecutting element 4, which is cut from the polymer tube 1 and as such, areintegral to the tube. Another example of this design may include aprovision for an element that would be positioned in the lumen afterremoval of the guidewire. This element would serve to deliver fluid forflushing. In this example, aspiration could be accomplished by applyingsuction to the proximal sheath such that fluid is removed as well asdebris while flushing is activated. While this embodiment is not shownin the figures, the present disclosure describes such configuration.

FIG. 12B details a moveable internal corewire 10 which extends down theinner lumen of the tube and is fastened to the distal tip of the device8 to provide a means for deploying the cutting and distal protectionelements through either expansion or contraction. Abrasives 6 mounted,coated or integral with the cutting element may be designed tofacilitate material removal and shaping of the lesion.

ID. Interventional Device

FIGS. 13A-13C show a Single Hypotube based design in which a “puff/pull”aspiration of the atherectomy debris is applied. A single hypotube of0.12 (0.10-0.14) mm with a 0.001″ thickness is laser cut and set toexpand an atherectomy device and distal protection device. The device isused by puffing saline or another inert liquid into the space whilesimultaneous (manually or mechanically) aspirating the disease area andapplying rotational force (pushing or turning, mechanically or manually)on the lesion. When fully deployed, the device is 1.4 millimeter inmaximum diameter.

E. Interventional Device

FIGS. 14A and 14B show a basket like atherectomy device, proximal to aPOBA/DE Balloon, proximal to a distal protection device. The basket likeatherectomy device and distal protection are deployed distal to thelesion. The device is pulled into the catheter, scrapping debris intothe basket. As the balloon passes the lesion site after atherectomy anangioplasty is applied, facilitating a smooth, non-striated bloodinterface.

IF. Interventional Device—Balloon Based

FIG. 15A depicts the device with the delivery sheath 3 covering theballoon catheter body 1 as well as the cutting 4 and distal protection 5elements, which are both integral with the balloon body cutting 4. Inanother example, there may be a provision for an element that would bepositioned in the lumen after removal of the guidewire. This elementwould serve to deliver fluid for flushing. In this example, aspirationcould be accomplished by applying suction to the proximal sheath suchthat fluid is removed as well as debris while flushing is activated.While this embodiment is not shown in the figures, the presentdisclosure describes such configuration. A guidewire 9 extends down theinner lumen of the device to provide a means for navigating the anatomy,

FIG. 15B depicts placement within the target anatomy, where theguidewire is removed and the sheath pulled back, exposing the cuttingand distal protection elements. Deployment of the distal elements iscontrolled by use of an inflation device to fill the balloon with fluid.Once the balloon is inflated, the profile would take shape such that thecutting and distal protection elements are deployed. Abrasives 6mounted, coated or integral with the cutting element may be designed tofacilitate material removal and shaping of the lesion.

Hydrogels or other material may be integral to the distal protectionelement 5 such that material is attracted and adheres to it.

FIGS. 16A-16C depict some general shapes for the balloon distalelements. These sketches serve to provide only general variation ideasand are not meant to be all inclusive.

IG. Interventional Device—OA Access Element

FIGS. 17A-17C show the use of a shaped guidewire to access the OA andfollow up with a guiding catheter to position within the entry to theOA. Once inside, the shaped guidewire will be exchanged for either astraight guidewire or an interventional device to continue theprocedure. FIGS. 17A-17C depict access of the OA by use of a shapedguidewire, entry into the OA by a guiding catheter over the shapedguidewire and finally exchange of the shaped guidewire for either astraight tip guidewire or an interventional device. The guidewire andguiding catheter is specifically designed for use in the OA and mayinclude a provision for providing downstream protection.

IH. Interventional Device—Flow Directed 1

FIG. 18 shows a device that will use the vascular flow to aid inlocating and positioning within the OA. There are several features thatare detailed here, but all share a common design element in that theyare specifically designed for the OA anatomy and will work with thevascular flow to aid in placement and positioning within the anatomy. Anadditional design provision may include the ability to work with the 10Pdevice (as detailed in section I). In this use, the flow directedelement would take into account the reversal of vascular flow and wouldfollow that flow accordingly, which would aid in the removal of thedevice from the target anatomy. This feature would simplify the removalof the instrument by reducing the amount of force required to withdrawthe device. There are several examples of this design as noted by FIG.18.

II. Interventional Device—Flow Directed 2

FIGS. 19-22 describe a simple, flow directed balloon that is unifiedwith a large volume delivery catheter. It is a hybridguidewire/balloon/aspiration device. Novelty is found in the fact thatthe flow directed balloon and guidewire are a single unit and that theinner diameter of the lumen starts out at around 7 to 8 French andnarrows dramatically for the last 3 cm to 4 cm.

Delivery of the device into the ostium of the OA may be done by acatheter, that has a 90 degree port at the ostium of the OA. This allowsfor the very small diameter (0.19 mm OD or smaller) balloon guidewire toenter into the OA and to be pulled into the artery and across the lesionby normal blood flow. The larger diameter of the inner diameter catheterallows for good pressure to be maintained proximal to the balloonfacilitating the delivery of contrast agents in addition to saline forballoon inflation.

IJ. 10P Device—General Description

FIGS. 23A-23E depict the an embodiment of the device used to manipulate10P. One element will fit the patients eye(s) such that it may be usedto apply pressure to the front of the eye. The eye portion may be heldin position with a strap, adhesive, external member or other method thatsufficiently accomplishes the task of keeping the eye portion in propercontact with the patient's eye(s). The eye contact portion of the devicemay be designed to cover and manipulate a single eye, both eyes, one ata time, two at the same time or any combination. Pressure manipulationof the front of the eye will be accomplished by applying a specifiedamount of direct pressure to the front (typically corneal) area of theeye. This may be accomplished in a variety of ways, including use ofpneumatic, hydraulic, gravity and/or other mechanical means ofmanipulating force over an area. There may be need to combine theseforces in such a way as to optimize the pressure manipulation. Use ofmechanical force manipulation will provide the best methodology andcontrol for removal of force such that the 10P returns to the normalsteady state post procedure in a repeatable, desirable manner. A secondelement will provide for the 10P measurement of the eye undermanipulation. There may be several ways to accomplish 10P measurement.These include remote implantable sensor with wired or wireless datatransmission capability, corneal tonometry, non-corneal tonometry and/ortranspalpebral tonometry. In addition, there may be other ways toaccomplish 10P measurements such that pressure values are obtained fromthe subject eye. A third element will provide the user (physician) withthe ability to select pressure and time for the device to interact withthe eye in the form of an external control feature. This externalcontrol feature may be in the form of a computer, tablet, smart phone orother device that provides the user with the necessary control andfeedback information needed to perform the 10P manipulation. Thiscontrol feature will also contain a feedback loop which willcontinuously monitor IOP so that a constant pressure may be maintained.This control mechanism will also allow for ramp up/ramp down ofpressure, non-constant pressure, time manipulation and/or anycombination thereof. This capability will likely be software driven andwill provide the user with the ability to custom tailor an 10Pmanipulation profile for a specific patient. Without intending to bebound by theory, the rate or pressure induced, time at pressure, andrate of pressure reduction will be important to the success of theprocedure and will design the control mechanism to provide thiscapability. In addition, the ability to capture, chart and store patientcentric data will be an element of this control mechanism.

Use of the device elements as detailed above will allow for thephysician to induce retrograde vascular flow for up to 3 minutes at atime, such that when the interventional device is used, the risk forretinal vasculature embolism is reduced. It is known that at a minimum,retrograde flow in the central retinal artery can be maintained forantithrombotic protection and possibly the ciliary arteries. Withpressure put on the front of the eye, the blood volume of the choroidlayers can be forced back, through the central retinal artery, ciliaryarteries and possibly lacrimal arteries.

FIGS. 24A and 24B detail how the force applied to the front of the eyewill translate into force flowing through the eye, increasing 10P,resulting in retrograde vascular flow. The drawing also details how theremoval of force will result in a return to the normal pressure state ofthe eye. Note the drawing is not anatomically correct.

FIG. 25 depicts one embodiment of a feedback loop utilizing animplantable 10P sensor.

FIG. 26 provides detail associated with the posterior vasculature of theeye for informational purposes only.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of an embodiment that is claimedor of what may be claimed, but rather as descriptions of featuresspecific to particular embodiments. Certain features that are describedin this specification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults.

While principles of the present disclosure are described herein withreference to illustrative aspects for particular applications, thedisclosure is not limited thereto. Those having ordinary skill in theart and access to the teachings provided herein will recognizeadditional modifications, applications, aspects, and substitution ofequivalents that all fall in the scope of the aspects described herein.Accordingly, the present disclosure is not to be considered as limitedby the foregoing description.

EXAMPLES Example 1

Without being bound by theory, it is believed that compromised bloodflow to the vasculature of the posterior eye directly contributes todiseases of the eye. Further, it is believed that this lack of normalblood flow may originate in the ICA, the OA, branches of the OA, have acardiac origin, and/or combinations thereof, and be directly caused by ablockage in one or more of these vessels. This lack of sufficient bloodflow directly contributes to inadequate nutrient levels seen in tissuessuch as the choroid, retina, optic nerve, and other ophthalmic anatomy.This blockage may manifest as stenosis, lesions, or other physiologywithin the ophthalmic related vasculature and compromise normal bloodflow such that the posterior eye vasculature does not receive anadequate nutrient supply for maintenance of normal function. As aresult, it is possible for a cascade of events to initiate which mayresult in various diseases of the eye.

Linear and volumetric blood flow was measured for healthy controls anddiseased patients, wherein the diseased patients had confirmed AMDdiagnoses. Flow rates were measured for the Left Ophthalmic Artery(LOA), Right Ophthalmic Artery (ROA), Left Internal Carotid Artery(LICA) and Right Internal Carotid Artery (RICA) using Phased ContrastMagnetic Resonance Imaging (PCMRI) technique on a 7 Tesla Nmri machine.These flow rates were measured in centimeters per second (cm/sec) forlinear flow and in millimeters/minute (ml/min) for volumetric flow. Theaverage diameter of the ICA for a healthy control is 4.6 mm and theaverage diameter of the OA for a healthy control is 1.2 mm. Averagevalues for the same vessels in diseased patients were 4.18 mm for theICA and 0.86 mm for the OA.

Specific linear and volumetric flow rates were compared, and the OA flowdata showed a medically or clinically observable difference between theflow rates for healthy controls compared to diseased patients. Specificflow rates were compared, and the ICA flow data shows a medically orclinically observable difference between the flow rates for healthycontrols compared to diseased patients. In every case, the blood flowrate for the diseased patients appeared to be lower than the blood flowrate for the healthy controls.

Example 2

In a cadaveric tissue, the RICA was removed and the ostium was visuallyexamined. Blockage of the OA at the ostium was confirmed, wherein theblockage appeared to be complete. Once the section of LICA was removed,internal access to the OA ostium was gained, and a micro PTCA ballooncatheter was inserted.

This test was performed to visually observe the effect of placing andinflating a balloon catheter in the OA. This (non-compliant) ballooncatheter had a maximum diameter of 0.85 mm at 16 atms, with a crossingprofile of 0.74 mm and a working length of approximately 5 mm. Theballoon was inflated several times to approximately 12 atms maximum andthe balloon was observed through the vessel. After observations, thevessel appeared to tolerate the inflations without obvious signs ofdamage.

Example 3

A system of the present disclosure is designed to induce reverse bloodflow in the cerebral vasculature during neuro interventional procedures.This system provides protection from particulate related stroke duringthese procedures. Enhancements to the basic system include:

CCA to IJV circuit. This pathway reduces the overall device lengthrequired to reach the target anatomy. While this procedure requirescervical access, there is no need to do femoral access and expose thepatient to the potential issues related to crossing the arch. This typeof connection between an artery and vein is commonly referred to as afistula.

Addition of an in line filter to capture particulate.

Sizing the tubing, stock cocks and filter such that a minimal resistanceto flow is encountered by blood as it travels through the device. It isanticipated the device will be 8.5 to 9.0 French. Maximizing theinternal diameter of the various components allows for blood to flow atthe most rapid velocity.

Addition of a circuit to connect the CCA flow to the SOA. Thisconnection will provide flow directly to the OA so that flow isreversed. This OA reverse flow will prevent embolization of theOA/central retinal artery during interventional procedures.

Specially designed CCA occlusion balloon designed to reduce probabilityof low or no flow zones in the CCA.

Example 4

In some embodiments of the present disclosure, the flow directionelement of the system is used to initiate the reversal of flow in theCCA. Typically, CCA flow reversal may be accomplished by use of aninflatable balloon device. CCA flow reversal may also be accomplishedwithout the need for a balloon by using a sheath that has external forceapplied to compress the CCA against the tube portion of the sheath. Thiscompressive action serves to prevent blood flow around the sheath, inthe same way as an inflatable balloon does from inside the CCA and forceblood through the sheath and into the venous circuit of the system,thereby providing flow reversal. The sheath may be of conventionaldesign, or may contain elements that facilitate compressing the CCAagainst the sheath for the purpose of establishing flow reversal.

Methodology and Purpose of Examples 5 and 6:

1) Dissection of specimens diagnosed with AMD for the purpose ofidentifying CAD disease (plaque) in the carotid siphon/ophthalmic ostiumand to provide evidence of the ability to cannulate and deliver anangioplasty balloon to the OA ostium.

2) Dissection of a specimen (with cervical segment) diagnosed with AMDto identify CAD disease (plaque) in the carotid siphon/ophthalmicostium.

A true endovascular approach requires an imaging modality that relies oninjection of contrast, which is not possible in static tissue samplessuch as a cadaver. Based on these limitations, the following twoExamples show balloon placement and inflation directly in the exposedophthalmic ostium in situ and post dissection.

Example 5

The primary goal for dissection of a specimen with bilateral AMD was toprove that it is possible to place and dilate an angioplasty ballooncatheter in the segment of the OA just distal to the ICA ostium, priorto the typical OA 90° bend, without dissecting the OA.

An angioplasty balloon with a maximum inflated diameter of 0.8 mm at 16ATMs, and a working length of approximately 3.5 mms was used.

The left and right ICA/OA ostiums in the first specimen were identifiedand material from the sphenoid was removed to expose the OA. The ballooncatheter was positioned into the LOA and the balloon was inserted suchthat the working length of the balloon did not extend beyond the desiredsegment of the LOA.

The balloon was able to be delivered and inflated at the desiredlocation of the LOA, within the ostium of the LOA.

Both ostiums were then examined for evidence of plaque in the ICA, OA,and ostium in situ. Plaque formation was identified at the ostium of thetransected LICA, and in the walls of the LICA. Plague formation was alsoidentified in the RICA, at the ostium of the transected ROA, and in thewalls of the RICA.

Example 6

The primary goal for dissection of this specimen was to prove that it ispossible to place and dilate an angioplasty balloon catheter in thesegment of the OA just distal to the ICA ostium, prior to the typical OA90° bend, without dissecting the OA. The secondary goal was to examineeach ICA/OA ostium for evidence of plaque. We identified the left andright ICA/OA ostiums without having to remove material from the sphenoidand could visualize plaque in both ICA segments in situ. In addition,plaque formation in the LOA could easily be seen.

The left and right ICA vessel segments were removed and transected. Inboth samples, blockage was observed directly at the ophthalmic ostium.

After examining the inside and outside of the LICA vessel, plaqueformation could clearly be seen at the base of the OA near the ostium.The LOA was dissected rom the LICA at the ostium to expose the plaque.Plaque formation was also clearly seen in the ostium of the LOA.

A balloon catheter was placed in the RICA vessel segment. The ballooncatheter was positioned into the ROA and inserted such that the workinglength of the balloon did not extend beyond the desired segment of theROA (as noted in the previous Example).

The angioplasty balloon was successfully positioned and inflated withinthe target ROA anatomy. Plaque was identified in both the LICA and RICAas well as both the ROA and LOA ostium. This plaque appeared to beblocking or nearly blocking the OA in both the left and right ostiums.

1-23. (canceled)
 24. A method, comprising: accessing a terminal branch of an ophthalmic artery through a skin of a head of a subject via a first device; positioning the first device or a second device within the ophthalmic artery of the subject; measuring a blood flow rate in the ophthalmic artery; and treating a blockage, a stenosis, a lesion, plaque, or other physiology in the ophthalmic artery or a junction between an internal carotid artery and the ophthalmic artery, wherein the treating includes increasing a size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery.
 25. The method of claim 24, wherein the accessing the terminal branch of the ophthalmic artery through the skin of the head of the subject includes accessing a supraorbital or supratrochlear artery of the subject via the first device.
 26. The method of claim 24, wherein the increasing the size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery includes removing material.
 27. The method of claim 24, wherein the increasing the size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery includes using a balloon in a balloon dilation procedure.
 28. The method of claim 24, wherein the measuring the blood flow rate in the ophthalmic artery includes measuring a linear blood flow rate.
 29. The method of claim 24, wherein the measuring the blood flow rate in the ophthalmic artery includes measuring a volumetric blood flow rate.
 30. The method of claim 24, further including stopping antegrade blood flow in the ophthalmic artery.
 31. A method, comprising: positioning a first device in a terminal branch of an ophthalmic artery through a skin of a head of a subject, wherein positioning the first device in the terminal branch of the ophthalmic artery through the skin includes positioning the first device in at least one of a supraorbital artery or a supratrochlear artery; and treating a blockage, a stenosis, a lesion, plaque, or other physiology in the ophthalmic artery or a junction between an internal carotid artery and the ophthalmic artery, wherein the treating includes increasing a blood flow rate in the ophthalmic artery.
 32. The method of claim 31, wherein the treating further includes increasing a size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery.
 33. The method of claim 32, wherein the increasing the size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery includes removing material.
 34. The method of claim 33, wherein the increasing the size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery includes using a balloon in a balloon dilatation procedure.
 35. The method of claim 33, wherein the increasing the size of the ophthalmic artery or the junction between the internal carotid artery and the ophthalmic artery includes using an atherectomy device in an atherectomy procedure.
 36. The method of claim 31, further including inducing retrograde blood flow in the ophthalmic artery.
 37. The method of claim 31, further including measuring a blood flow rate in the ophthalmic artery.
 38. The method of claim 37, wherein the measuring the blood flow rate in the ophthalmic artery includes measuring a linear blood flow rate.
 39. The method of claim 37, wherein the measuring the blood flow rate in the ophthalmic artery includes measuring a volumetric blood flow rate.
 40. A method, comprising: locating a site in an arterial blood supply to an eye that compromises blood flow and contributes to an eye disorder; accessing a terminal branch of an ophthalmic artery through a skin of a head of a subject via a first device; delivering the first device or a second device intravascularly to the site; and treating the site with the first device or the second device, wherein the site is located in the ophthalmic artery or a junction between an internal carotid artery and the ophthalmic artery.
 41. The method of claim 40, further including stopping antegrade blood flow in the ophthalmic artery or inducing retrograde blood flow in the ophthalmic artery.
 42. The method of claim 41, further including measuring the blood flow rate in the ophthalmic artery, including measuring at least one of a linear blood flow rate or a volumetric blood flow rate.
 43. The method of claim 40, wherein treating the site includes using a balloon in a balloon dilation procedure and/or using an atherectomy device in an atherectomy procedure. 